MAK MAY SUNG (CN)
CHAN PUI-KWONG (US)
MAK MAY SUNG (CN)
| WO2011009032A1 | 2011-01-20 |
| What is claimed is: 1 . A compound selected from the structure: wherein R1 , R2, R3, R4, R5, R8, R9, R10, R1 1 , R12, R13, R14, R15 are independently selected from the group of CH3, CH20H, COOH, hydrogen, hydroxyl, methyl, O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, O- 3,3-Dimethylartyloyl, O-Cinnamoyl, O-Pentenoyl, O-Hexanoyl, 0-benzoyl, O- Ethylbutyryl,O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O- alkenylcarbonyl, O-alkane, O-alkene, O-sugar moiety, O-ethanoyl, O-propanoyl, O-propenoyl, O-butanoyl, O-butenoyl, O-pentanoyl, O-hexenoyl, O-heptanoyl, O- heptenoyl, O-octanoyl, O-octenoyl, O-nonanoyl, O-nonenoyl, O-decanoyl, O- decenoyl, O-propionyl, O-2-propenoyl, O-2-butenoyl, O-lsobutyryl, O-2- methylpropanoyl, O-2-ethylbutyryl, O-ethylbutanoyl, O-2-ethylbutanoyl, O-butyryl, O- (E)-2,3-Dimethylacryloyl, O-(E)-2-Methylcrotonoyl, O-3-c/s-Methyl- methacryloyl, O-3-Methyl-2-butenoyl, O-3-Methylcrotonoyl, O-4-Pentenoyl, O- (2E)-2-pentenoyl, O-Caproyl, O-5-Hexenoyl, O-Capryloyl, O-Lauroyl, O- Dodecanoyl, O-Myristoyl, O-Tetradecanoyl, O-Oleoyl, O-C(2-18) Acyl, CH2O- angeloyl, CH2O-tigloyl, CH2O-senecioyl, CH2O-acetyl, CH2O-Crotonoyl, CH2O- 3,3-Dimethylartyloyl, CH2O-Cinnamoyl, CH2O-Pentenoyl, CH2O-Hexanoyl, CH2O-benzoyl, CH2O-Ethylbutyryl, CH3, CH2OH, CH2O-alkyl, CH2O-dibenzoyl, CH2O-benzoyl, CH2O-alkanoyl, CH2O-alkenoyl, CH2O-benzoyl alkyl substituted O-alkanoyl, CH2O-alkanoyl substituted phenyl, CH2O-alkenoyl substituted phenyl, CH2O-aryl, CH2O-acyl, CH2O-heterocylic, CH2O-heteroraryl, CH2O- alkenylcarbonyl, CH2O-ethanoyl, CH2O-propanoyl, CH2O-propenoyl, CH2O- butanoyl, CH2O-butenoyl, CH2O-pentanoyl, CH2O-hexenoyl, CH2O-heptanoyl, CH2O-heptenoyl, CH2O-octanoyl, CH2O-octenoyl, CH2O-nonanoyl, CH2O- nonenoyl, CH2O-decanoyl, CH2O-decenoyl, CH2O-propionyl, CH2O-2- propenoyl, CH2O-2-butenoyl, CH20-lsobutyryl, CH2O-2-methylpropanoyl, CH2O-2-ethylbutyryl, CH2O-ethylbutanoyl, CH2O-2-ethylbutanoyl, CH2O-butyryl, CH2O-(E)-2,3-Dimethylacryloyl, CH2O-(E)-2-Methylcrotonoyl, CH20-3-C/S- Methyl-methacryloyl, CH2O-3-Methyl-2-butenoyl, CH2O-3-Methylcrotonoyl, CH2O-4-Pentenoyl, CH2O-(2E)-2-pentenoyl, CH2O-Caproyl, CH2O-5-Hexenoyl, CH2O-Capryloyl, CH2O-Lauroyl, CH2O-Dodecanoyl, CH2O-Myristoyl, CH20- Tetradecanoyl, CH2O-Oleoyl, CH20-C(2-18) Acyl, or derivatives thereof; or wherein the structure (2A) comprises at least 2 groups selected from CH3, CH20H, COOH , hydrogen, hydroxyl, methyl, O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, 0-3,3-Dimethylartyloyl, O-Cinnamoyl, O-Pentenoyl, O- Hexanoyl, 0-benzoyl, O-Ethylbutyryl,O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O- heteroraryl, O-alkenylcarbonyl, O-alkane, O-alkene, O-sugar moiety, O-ethanoyl, O-propanoyl, O-propenoyl, O-butanoyl, O-butenoyl, O-pentanoyl, O-hexenoyl, O- heptanoyl, O-heptenoyl, O-octanoyl, O-octenoyl, O-nonanoyl, O-nonenoyl, O- decanoyl, O-decenoyl, O-propionyl, O-2-propenoyl, O-2-butenoyl, O-lsobutyryl, O-2-methylpropanoyl, O-2-ethylbutyryl, O-ethylbutanoyl, O-2-ethylbutanoyl, O- butyryl, O- (E)-2,3-Dimethylacryloyl, O-(E)-2-Methylcrotonoyl, O-3-c/s-Methyl- methacryloyl, O-3-Methyl-2-butenoyl, O-3-Methylcrotonoyl, O-4-Pentenoyl, O- (2E)-2-pentenoyl, O-Caproyl, O-5-Hexenoyl, O-Capryloyl, O-Lauroyl, O- Dodecanoyl, O-Myristoyl, O-Tetradecanoyl, O-Oleoyl, O-C(2-18) Acyl, CH2O- sugar moiety, CH2O-angeloyl, CH2O-tigloyl, CH2O-senecioyl, CH2O-acetyl, CH2O-Crotonoyl, CH2O-3,3-Dimethylartyloyl, CH2O-Cinnamoyl, CH2O- Pentenoyl, CH2O-Hexanoyl, CH2O-benzoyl, CH2O-Ethylbutyryl, CH3, CH2OH, CH2O-alkyl, CH2O-dibenzoyl, CH2O-benzoyl, CH2O-alkanoyl, CH2O-alkenoyl, CH2O-benzoyl alkyl substituted O-alkanoyl, CH2O-alkanoyl substituted phenyl, CH2O-alkenoyl substituted phenyl, CH2O-aryl, CH2O-acyl, CH2O-heterocylic, CH2O-heteroraryl, CH2O-alkenylcarbonyl, CH2O-ethanoyl, CH2O-propanoyl, CH2O-propenoyl, CH2O-butanoyl, CH2O-butenoyl, CH2O-pentanoyl, CH2O- hexenoyl, CH2O-heptanoyl, CH2O-heptenoyl, CH2O-octanoyl, CH2O-octenoyl, CH2O-nonanoyl, CH2O-nonenoyl, CH2O-decanoyl, CH2O-decenoyl, CH2O- propionyl, CH2O-2-propenoyl, CH2O-2-butenoyl, CH2O-lsobutyryl, CH2O-2- methylpropanoyl, CH2O-2-ethylbutyryl, CH2O-ethylbutanoyl, CH2O-2- ethylbutanoyl, CH2O-butyryl, CH2O-(E)-2,3-Dimethylacryloyl, CH2O-(E)-2- Methylcrotonoyl, CH2O-3-c/'s-Methyl-methacryloyl, CH2O-3-Methyl-2-butenoyl, CH2O-3-Methylcrotonoyl, CH2O-4-Pentenoyl, CH20-(2E)-2-pentenoyl, CH20- Caproyl, CH2O-5-Hexenoyl, CH2O-Capryloyl, CH2O-Lauroyl, CH20- Dodecanoyl, CH2O-Myristoyl, CH2O-Tetradecanoyl, CH2O-Oleoyl, CH20-C(2- 18) Acyl, ; or wherein wherein the R1 and R2 are attached OH; or wherein R4, R10 are attached a CH2O-angeloyl, CH2O-tigloyl, CH2O-senecioyl, CH2O-acetyl, CH2O-Crotonoyl, CH2O-3,3-Dimethylartyloyl, CH2O-Cinnamoyl, CH2O- Pentenoyl, CH2O-Hexanoyl, CH2O-benzoyl, CH2O-Ethylbutyryl, CH3, CH2OH, CH2O-alkyl, CH2O-dibenzoyl, CH2O-benzoyl, CH2O-alkanoyl, CH2O-alkenoyl, CH2O-benzoyl alkyl substituted O-alkanoyl, CH2O-alkanoyl substituted phenyl, CH2O-alkenoyl substituted phenyl, CH2O-aryl, CH2O-acyl, CH2O-heterocylic, CH2O-heteroraryl, CH2O-alkenylcarbonyl, CH2O-ethanoyl, CH2O-propanoyl, CH2O-propenoyl, CH2O-butanoyl, CH2O-butenoyl, CH2O-pentanoyl, CH2O- hexenoyl, CH2O-heptanoyl, CH2O-heptenoyl, CH2O-octanoyl, CH2O-octenoyl, CH2O-nonanoyl, CH2O-nonenoyl, CH2O-decanoyl, CH2O-decenoyl, CH2O- propionyl, CH2O-2-propenoyl, CH2O-2-butenoyl, CH2O-lsobutyryl, CH2O-2- methylpropanoyl, CH2O-2-ethylbutyryl, CH2O-ethylbutanoyl, CH2O-2- ethylbutanoyl, CH2O-butyryl, CH2O-(E)-2,3-Dimethylacryloyl, CH2O-(E)-2- Methylcrotonoyl, CH2O-3-c/'s-Methyl-methacryloyl, CH2O-3-Methyl-2-butenoyl, CH2O-3-Methylcrotonoyl, CH2O-4-Pentenoyl, CH2O-(2E)-2-pentenoyl, CH2O- Caproyl, CH2O-5-Hexenoyl, CH2O-Capryloyl, CH2O-Lauroyl, CH2O- Dodecanoyl, CH2O-Myristoyl, CH2O-Tetradecanoyl, CH2O-Oleoyl, CH2O-C(2- 18) Acyl, I; wherein the R3 and R8 is hydrogen or hydroxyl; wherein the R9, R1 1 , R12, R13, R14, R15 are independently attached with a methyl; wherein R3 is H, OH or absent; wherein R8 is H or OH; wherein R16 is H, CH3, OH ,or R4 and R16 may together form -CH2-X-, CH(OH)-X- or C(=O)-X-, wherein the -X- may be O or NH or S; wherein when the C12-13 of ring 3 of the triterpene has a double bond then R16 is absent; or wherein R10 is CH2O-angeloyl, CH2O-tigloyl, CH2O-senecioyl, CH2O-acetyl, CH2O-Crotonoyl, CH2O-3,3-Dimethylartyloyl, CH2O-Cinnamoyl, CH2O-Pentenoyl, CH2O-Hexanoyl, CH2O-benzoyl, or CH2O- Ethylbutyryl; CH2O-alkanoyl, CH2O-alkenoyl, CH2O-benzoyl alkyl substituted O- alkanoyl, CH2O-alkanoyl substituted phenyl, CH2O-alkenoyl substituted phenyl, CH2O-aryl, CH2O-acyl, CH2O-heterocylic, CH2O-heteroraryl, CH2O- alkenylcarbonyl, CH2O-ethanoyl, CH2O-propanoyl, CH2O-propenoyl, CH2O- butanoyl, CH2O-butenoyl, CH2O-pentanoyl, CH2O-hexenoyl, CH2O-heptanoyl, CH2O-heptenoyl, CH2O-octanoyl, CH2O-octenoyl, CH2O-nonanoyl, CH2O- nonenoyl, CH2O-decanoyl, CH2O-decenoyl, CH2O-propionyl, CH2O-2- propenoyl, CH2O-2-butenoyl, CH20-lsobutyryl, CH2O-2-methylpropanoyl, CH2O-2-ethylbutyryl, CH2O-ethylbutanoyl, CH2O-2-ethylbutanoyl, CH2O-butyryl, CH2O-(E)-2,3-Dimethylacryloyl, CH2O-(E)-2-Methylcrotonoyl, CH20-3-C/S- Methyl-methacryloyl, CH2O-3-Methyl-2-butenoyl, CH2O-3-Methylcrotonoyl, CH2O-4-Pentenoyl, CH2O-(2E)-2-pentenoyl, CH2O-Caproyl, CH2O-5-Hexenoyl, CH2O-Capryloyl, CH2O-Lauroyl, CH2O-Dodecanoyl, CH2O-Myristoyl, CH20- Tetradecanoyl, CH2O-Oleoyl, CH20-C(2-18) Acyl; R1 , R2, R3, R4, R5, R8, R9, R10, R1 1 , R12, R13, R14 or R15 comprise of one or more acids or at least 1 , or 2, or 3, or 4 of R1 , R2, R3, R4, R5, R8, R9, R10, R1 1 , R12, R13, R14 and R15 is hydroxyl; or at least 2, or 3, or 4, or 5, or 6, or 7 of R1 , R2, R3, R4, R5, R8, R9, R10, R1 1 , R12, R13, R14 and R15 are independently attached a group selected from the group of O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, O- 3,3-Dimethylartyloyl, O-Cinnamoyl, O-Pentenoyl, O-Hexanoyl, O-benzoyI, O- Ethylbutyryl,O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O- alkenylcarbonyl, O-alkane, O-alkene, O-sugar moiety, O-ethanoyl, O-propanoyl, O-propenoyl, O-butanoyl, O-butenoyl, O-pentanoyl, O-hexenoyl, O-heptanoyl, O- heptenoyl, O-octanoyl, O-octenoyl, O-nonanoyl, O-nonenoyl, O-decanoyl, O- decenoyl, O-propionyl, O-2-propenoyl, O-2-butenoyl, O-lsobutyryl, O-2- methylpropanoyl, O-2-ethylbutyryl, O-ethylbutanoyl, O-2-ethylbutanoyl, O-butyryl, O- (E)-2,3-Dimethylacryloyl, O-(E)-2-Methylcrotonoyl, O-3-c/s-Methyl- methacryloyl, O-3-Methyl-2-butenoyl, O-3-Methylcrotonoyl, O-4-Pentenoyl, O- (2E)-2-pentenoyl, O-Caproyl, O-5-Hexenoyl, O-Capryloyl, O-Lauroyl, O- Dodecanoyl, O-Myristoyl, O-Tetradecanoyl, O-Oleoyl, O-C(2-18) Acyl, , CH2O- angeloyl, CH2O-tigloyl, CH2O-senecioyl, CH2O-acetyl, CH2O-Crotonoyl, CH2O- 3,3-Dimethylartyloyl, CH2O-Cinnamoyl, CH2O-Pentenoyl, CH2O-Hexanoyl, CH2O-benzoyl, CH2O-Ethylbutyryl, CH3, CH2OH, CH2O-alkyl, CH2O-dibenzoyl, CH2O-benzoyl, CH2O-alkanoyl, CH2O-alkenoyl, CH2O-benzoyl alkyl substituted O-alkanoyl, CH2O-alkanoyl substituted phenyl, CH2O-alkenoyl substituted phenyl, CH2O-aryl, CH2O-acyl, CH2O-heterocylic, CH2O-heteroraryl, CH2O- alkenylcarbonyl, CH2O-ethanoyl, CH2O-propanoyl, CH2O-propenoyl, CH2O- butanoyl, CH2O-butenoyl, CH2O-pentanoyl, CH2O-hexenoyl, CH2O-heptanoyl, CH2O-heptenoyl, CH2O-octanoyl, CH2O-octenoyl, CH2O-nonanoyl, CH2O- nonenoyl, CH2O-decanoyl, CH2O-decenoyl, CH2O-propionyl, CH2O-2- propenoyl, CH2O-2-butenoyl, CH2O-lsobutyryl, CH2O-2-methylpropanoyl, CH2O-2-ethylbutyryl, CH2O-ethylbutanoyl, CH2O-2-ethylbutanoyl, CH2O-butyryl, CH2O-(E)-2,3-Dimethylacryloyl, CH2O-(E)-2-Methylcrotonoyl, CH20-3-C/S- Methyl-methacryloyl, CH2O-3-Methyl-2-butenoyl, CH2O-3-Methylcrotonoyl, CH2O-4-Pentenoyl, CH2O-(2E)-2-pentenoyl, CH2O-Caproyl, CH2O-5-Hexenoyl, CH2O-Capryloyl, CH2O-Lauroyl, CH2O-Dodecanoyl, CH2O-Myristoyl, CH20- Tetradecanoyl, CH2O-Oleoyl, CH20-C(2-1 8) Acyl and derivatives thereof, wherein the group is attached to the triterpene directly or by connecting moiety(ies); wherein R10 and at least 1 or 2, or 3, or 4, or 5, or 6, or 7 of R1 , R2, R3, R4, R5, and R8 are independently attached a group selected from the group of O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, 0-3,3- Dimethylartyloyl, O-Cinnamoyl, O-Pentenoyl, O-Hexanoyl, O-benzoyl, O- Ethylbutyryl,O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O- alkenylcarbonyl, O-alkane, O-alkene, O-sugar moiety, O-ethanoyl, O-propanoyl, O-propenoyl, O-butanoyl, O-butenoyl, O-pentanoyl, O-hexenoyl, O-heptanoyl, O- heptenoyl, O-octanoyl, O-octenoyl, O-nonanoyl, O-nonenoyl, O-decanoyl, O- decenoyl, O-propionyl, O-2-propenoyl, O-2-butenoyl, O-lsobutyryl, O-2- methylpropanoyl, O-2-ethylbutyryl, O-ethylbutanoyl, O-2-ethylbutanoyl, O-butyryl, O- (E)-2,3-Dimethylacryloyl, O-(E)-2-Methylcrotonoyl, O-3-c/s-Methyl- methacryloyl, O-3-Methyl-2-butenoyl, O-3-Methylcrotonoyl, O-4-Pentenoyl, O- (2E)-2-pentenoyl, O-Caproyl, O-5-Hexenoyl, O-Capryloyl, O-Lauroyl, O- Dodecanoyl, O-Myristoyl, O-Tetradecanoyl, O-Oleoyl, O-C(2-18) Acyl, CH2O- angeloyl, CH2O-tigloyl, CH2O-senecioyl, CH2O-acetyl, CH2O-Crotonoyl, CH2O- 3,3-Dimethylartyloyl, CH2O-Cinnamoyl, CH2O-Pentenoyl, CH2O-Hexanoyl, CH2O-benzoyl, CH2O-Ethylbutyryl, CH3, CH2OH, CH2O-alkyl, CH2O-dibenzoyl, CH2O-benzoyl, CH2O-alkanoyl, CH2O-alkenoyl, CH2O-benzoyl alkyl substituted O-alkanoyl, CH2O-alkanoyl substituted phenyl, CH2O-alkenoyl substituted phenyl, CH2O-aryl, CH2O-acyl, CH2O-heterocylic, CH2O-heteroraryl, CH2O- alkenylcarbonyl, CH2O-ethanoyl, CH2O-propanoyl, CH2O-propenoyl, CH2O- butanoyl, CH2O-butenoyl, CH2O-pentanoyl, CH2O-hexenoyl, CH2O-heptanoyl, CH2O-heptenoyl, CH2O-octanoyl, CH2O-octenoyl, CH2O-nonanoyl, CH2O- nonenoyl, CH2O-decanoyl, CH2O-decenoyl, CH2O-propionyl, CH2O-2- propenoyl, CH2O-2-butenoyl, CH2O-lsobutyryl, CH2O-2-methylpropanoyl, CH2O-2-ethylbutyryl, CH2O-ethylbutanoyl, CH2O-2-ethylbutanoyl, CH2O-butyryl, CH2O-(E)-2,3-Dimethylacryloyl, CH2O-(E)-2-Methylcrotonoyl, CH2O-3-C/S- Methyl-methacryloyl, CH2O-3-Methyl-2-butenoyl, CH2O-3-Methylcrotonoyl, CH2O-4-Pentenoyl, CH2O-(2E)-2-pentenoyl, CH2O-Caproyl, CH2O-5-Hexenoyl, CH2O-Capryloyl, CH2O-Lauroyl, CH2O-Dodecanoyl, CH2O-Myristoyl, CH2O- Tetradecanoyl, CH2O-Oleoyl, CH2O-C(2-18) Acyl, and derivatives thereof. : R1 , R2, R3, R4, R5, R8, R9, R10, R1 1 , R12, R13, R14, R15 are independently selected from the group of CH3, CH2OH, COOH , hydrogen, hydroxyl, methyl, O- angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, O-3,3-Dimethylartyloyl, O-Cinnamoyl, O-Pentenoyl, O-Hexanoyl, O-benzoyl, O-Ethylbutyryl,O-alkyl, O- dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O- alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O- acyl, O-heterocylic, O-heteroraryl, O-alkenylcarbonyl, O-alkane, O-alkene, O- sugar moiety, O-ethanoyl, O-propanoyl, O-propenoyl, O-butanoyl, O-butenoyl, O- pentanoyl, O-hexenoyl, O-heptanoyl, O-heptenoyl, O-octanoyl, O-octenoyl, O- nonanoyl, O-nonenoyl, O-decanoyl, O-decenoyl, O-propionyl, O-2-propenoyl, O- 2-butenoyl, O-lsobutyryl, O-2-methylpropanoyl, O-2-ethylbutyryl, O-ethylbutanoyl, O-2-ethylbutanoyl, O-butyryl, O- (E)-2,3-Dimethylacryloyl, O-(E)-2- Methylcrotonoyl, O-3-c/s-Methyl-methacryloyl, O-3-Methyl-2-butenoyl, O-3- Methylcrotonoyl, O-4-Pentenoyl, O-(2E)-2-pentenoyl, O-Caproyl, O-5-Hexenoyl, O-Capryloyl, O-Lauroyl, O-Dodecanoyl, O-Myristoyl, O-Tetradecanoyl, O-Oleoyl, O-C(2-18) Acyl, CH2O-alkane, CH2O-alkene and CH2O-sugar moiety, CH2O- angeloyl, CH2O-tigloyl, CH2O-senecioyl, CH2O-acetyl, CH2O-Crotonoyl, CH2O- 3,3-Dimethylartyloyl, CH2O-Cinnamoyl, CH2O-Pentenoyl, CH2O-Hexanoyl, CH2O-benzoyl, CH2O-Ethylbutyryl, CH3, CH2OH, CH2O-alkyl, CH2O-dibenzoyl, CH2O-benzoyl, CH2O-alkanoyl, CH2O-alkenoyl, CH2O-benzoyl alkyl substituted O-alkanoyl, CH2O-alkanoyl substituted phenyl, CH2O-alkenoyl substituted phenyl, CH2O-aryl, CH2O-acyl, CH2O-heterocylic, CH2O-heteroraryl, CH2O- alkenylcarbonyl, CH2O-ethanoyl, CH2O-propanoyl, CH2O-propenoyl, CH2O- butanoyl, CH2O-butenoyl, CH20-pentanoyl, CH2O-hexenoyl, CH2O-heptanoyl, CH2O-heptenoyl, CH2O-octanoyl, CH2O-octenoyl, CH2O-nonanoyl, CH20- nonenoyl, CH2O-decanoyl, CH2O-decenoyl, CH20-propionyl, CH20-2- propenoyl, CH2O-2-butenoyl, CH20-lsobutyryl, CH2O-2-methylpropanoyl, CH2O-2-ethylbutyryl, CH2O-ethylbutanoyl, CH2O-2-ethylbutanoyl, CH2O-butyryl, CH2O-(E)-2,3-Dimethylacryloyl, CH2O-(E)-2-Methylcrotonoyl, CH20-3-C/S- Methyl-methacryloyl, CH20-3-Methyl-2-butenoyl, CH20-3-Methylcrotonoyl, CH20-4-Pentenoyl, CH20-(2E)-2-pentenoyl, CH20-Caproyl, CH20-5-Hexenoyl, CH20-Capryloyl, CH20-Lauroyl, CH20-Dodecanoyl, CH20-Myristoyl, CH20- Tetradecanoyl, CH20-Oleoyl, CH20-C(2-18) Acyl, (CnH2n)0-angeloyl, (CnH2n)0-tigloyl, (CnH2n)0-senecioyl, (CnH2n)0-acetyl, (CnH2n)0-Crotonoyl, (CnH2n)0-3,3-Dimethylartyloyl, (CnH2n)0-Cinnamoyl, (CnH2n)0-Pentenoyl, (CnH2n)0-Hexanoyl, (CnH2n)0-benzoyl, (CnH2n)0-Ethylbutyryl, (CnH2n)0- alkyl, (CnH2n)0-dibenzoyl, (CnH2n)0-benzoyl, (CnH2n)0-alkanoyl, (CnH2n)0- alkenoyl, (CnH2n)0-benzoyl alkyl substituted O-alkanoyl, (CnH2n)0-alkanoyl substituted phenyl, (CnH2n)0-alkenoyl substituted phenyl, (CnH2n)0-aryl, (CnH2n)0-acyl, (CnH2n)0-heterocylic, (CnH2n)0-heteroraryl, (CnH2n)0- alkenylcarbonyl, (CnH2n)0-alkane, (CnH2n)0-alkene and (CnH2n)0-sugar moiety, wherein n is 1 or 2 or 3 or 4 or over 5; or wherein any 1 or 2 or 3 or 4 of R1 , R2, R3, R4, R5, R8 and R10 are independently attached an O-angeloyl, O- tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, 0-3,3-Dimethylartyloyl, O-Cinnamoyl, O-Pentenoyl, O-Hexanoyl, O-benzoyl, 0-Ethylbutyryl,0-alkyl, O-dibenzoyl, O- benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O- alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O- heterocylic, O-heteroraryl, O-alkenylcarbonyl, O-ethanoyl, O-propanoyl, O- propenoyl, O-butanoyl, O-butenoyl, O-pentanoyl, O-hexenoyl, O-heptanoyl, O- heptenoyl, O-octanoyl, O-octenoyl, O-nonanoyl, O-nonenoyl, O-decanoyl, O- decenoyl, O-propionyl, O-2-propenoyl, O-2-butenoyl, O-lsobutyryl, O-2- methylpropanoyl, O-2-ethylbutyryl, O-ethylbutanoyl, O-2-ethylbutanoyl, O-butyryl, O-(E)-2,3-Dimethylacryloyl, O-(E)-2-Methylcrotonoyl, O-3-c/s-Methyl- methacryloyl, O-3-Methyl-2-butenoyl, O-3-Methylcrotonoyl, O-4-Pentenoyl, O- (2E)-2-pentenoyl, O-Caproyl, O-5-Hexenoyl, O-Capryloyl, O-Lauroyl, O- Dodecanoyl, O-Myristoyl, O-Tetradecanoyl, O-Oleoyl, O-C(2-18) Acyl, CH2O- angeloyl, CH2O-tigloyl, CH2O-senecioyl, CH2O-acetyl, CH2O-Crotonoyl, CH2O- 3,3-Dimethylartyloyl, CH2O-Cinnamoyl, CH2O-Pentenoyl, CH2O-Hexanoyl, CH2O-benzoyl, CH2O-Ethylbutyryl, CH3, CH2OH, CH2O-alkyl, CH2O-dibenzoyl, CH2O-benzoyl, CH2O-alkanoyl, CH2O-alkenoyl, CH20-benzoyl alkyl substituted O-alkanoyl, CH20-alkanoyl substituted phenyl, CH20-alkenoyl substituted phenyl, CH20-aryl, CH20-acyl, CH20-heterocylic, CH20-heteroraryl, CH20- alkenylcarbonyl, CH20-ethanoyl, CH20-propanoyl, CH20-propenoyl, CH20- butanoyl, CH20-butenoyl, CH20-pentanoyl, CH20-hexenoyl, CH20-heptanoyl, CH20-heptenoyl, CH20-octanoyl, CH20-octenoyl, CH20-nonanoyl, CH20- nonenoyl, CH20-decanoyl, CH20-decenoyl, CH20-propionyl, CH20-2- propenoyl, CH20-2-butenoyl, CH20-lsobutyryl, CH20-2-methylpropanoyl, CH20-2-ethylbutyryl, CH20-ethylbutanoyl, CH20-2-ethylbutanoyl, CH20-butyryl, CH20-(E)-2,3-Dimethylacryloyl, CH20-(E)-2-Methylcrotonoyl, CH20-3-C/S- Methyl-methacryloyl, CH20-3-Methyl-2-butenoyl, CH20-3-Methylcrotonoyl, CH20-4-Pentenoyl, CH20-(2E)-2-pentenoyl, CH20-Caproyl, CH20-5-Hexenoyl, CH20-Capryloyl, CH20-Lauroyl, CH20-Dodecanoyl, CH20-Myristoyl, CH20- Tetradecanoyl, CH20-Oleoyl, CH20-C(2-18) Acyl; or wherein R9, R1 1 , R12, R13, R14, R15 are independently attached a CH3; or wherein R10 is attached an O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, 0-3,3-Dimethylartyloyl, O-Cinnamoyl, O-Pentenoyl, O-Hexanoyl, O-benzoyl, 0-Ethylbutyryl,0-alkyl, O- dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O- alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O- acyl, O-heterocylic, O-heteroraryl, O-alkenylcarbonyl, O-ethanoyl, O-propanoyl, O-propenoyl, O-butanoyl, O-butenoyl, O-pentanoyl, O-hexenoyl, O-heptanoyl, O- heptenoyl, O-octanoyl, O-octenoyl, O-nonanoyl, O-nonenoyl, O-decanoyl, O- decenoyl, O-propionyl, O-2-propenoyl, O-2-butenoyl, O-lsobutyryl, O-2- methylpropanoyl, O-2-ethylbutyryl, O-ethylbutanoyl, O-2-ethylbutanoyl, O-butyryl, O- (E)-2,3-Dimethylacryloyl, O-(E)-2-Methylcrotonoyl, O-3-c/s-Methyl- methacryloyl, O-3-Methyl-2-butenoyl, O-3-Methylcrotonoyl, O-4-Pentenoyl, O- (2E)-2-pentenoyl, O-Caproyl, O-5-Hexenoyl, O-Capryloyl, O-Lauroyl, O- Dodecanoyl, O-Myristoyl, O-Tetradecanoyl, O-Oleoyl, O-C(2-18) Acyl, CH2O- angeloyl, CH2O-tigloyl, CH2O-senecioyl, CH2O-acetyl, CH2O-Crotonoyl, CH2O- 3,3-Dimethylartyloyl, CH2O-Cinnamoyl, CH2O-Pentenoyl, CH2O-Hexanoyl, CH2O-benzoyl, CH2O-Ethylbutyryl, CH3, CH2OH, CH2O-alkyl, CH2O-dibenzoyl, CH2O-alkanoyl, CH2O-alkenoyl, CH2O-benzoyl alkyl substituted O-alkanoyl, CH2O-alkanoyl substituted phenyl, CH2O-alkenoyl substituted phenyl, CH2O- aryl, CH2O-acyl, CH2O-heterocylic, CH2O-heteroraryl, CH2O-alkenylcarbonyl, CH2O-ethanoyl, CH2O-propanoyl, CH2O-propenoyl, CH2O-butanoyl, CH2O- butenoyl, CH2O-pentanoyl, CH2O-hexenoyl, CH2O-heptanoyl, CH2O-heptenoyl, CH2O-octanoyl, CH2O-octenoyl, CH20-nonanoyl, CH2O-nonenoyl, CH20- decanoyl, CH2O-decenoyl, CH20-propionyl, CH2O-2-propenoyl, CH20-2- butenoyl, CH2O-lsobutyryl, CH2O-2-methylpropanoyl, CH2O-2-ethylbutyryl, CH2O-ethylbutanoyl, CH2O-2-ethylbutanoyl, CH2O-butyryl, CH2O-(E)-2,3- Dimethylacryloyl, CH2O-(E)-2-Methylcrotonoyl, CH2O-3-c/s-Methyl-methacryloyl, CH2O-3-Methyl-2-butenoyl, CH2O-3-Methylcrotonoyl, CH2O-4-Pentenoyl, CH2O-(2E)-2-pentenoyl, CH2O-Caproyl, CH20-5-Hexenoyl, CH20-Capryloyl, CH20-Lauroyl, CH20-Dodecanoyl, CH20-Myristoyl, CH20-Tetradecanoyl, CH20-Oleoyl, CH20-C(2-18) Acyl; or wherein R4 and R10 are independently attached an O-angeloyl, O-tigloyl, O- senecioyl, O-acetyl, O-Crotonoyl, 0-3,3-Dimethylartyloyl, O-Cinnamoyl, O- Pentenoyl, O-Hexanoyl, O-benzoyl, O-Ethylbutyryl, O-alkyl, O-dibenzoyl, O- benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O- alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O- heterocylic, O-heteroraryl, O-alkenylcarbonyl, O-ethanoyl, O-propanoyl, O- propenoyl, O-butanoyl, O-butenoyl, O-pentanoyl, O-hexenoyl, O-heptanoyl, O- heptenoyl, O-octanoyl, O-octenoyl, O-nonanoyl, O-nonenoyl, O-decanoyl, O- decenoyl, O-propionyl, O-2-propenoyl, O-2-butenoyl, O-lsobutyryl, O-2- methylpropanoyl, O-2-ethylbutyryl, O-ethylbutanoyl, O-2-ethylbutanoyl, O-butyryl, O- (E)-2,3-Dimethylacryloyl, O-(E)-2-Methylcrotonoyl, O-3-c/s-Methyl- methacryloyl, O-3-Methyl-2-butenoyl, O-3-Methylcrotonoyl, O-4-Pentenoyl, O- (2E)-2-pentenoyl, O-Caproyl, O-5-Hexenoyl, O-Capryloyl, O-Lauroyl, O- Dodecanoyl, O-Myristoyl, O-Tetradecanoyl, O-Oleoyl, O-C(2-18) Acyl, CH2O- angeloyl, CH2O-tigloyl, CH2O-senecioyl, CH2O-acetyl, CH2O-Crotonoyl, CH2O- 3,3-Dimethylartyloyl, CH2O-Cinnamoyl, CH2O-Pentenoyl, CH2O-Hexanoyl, CH2O-benzoyl, CH2O-Ethylbutyryl, CH3, CH2OH, CH2O-alkyl, CH2O-dibenzoyl, CH2O-benzoyl, CH2O-alkanoyl, CH2O-alkenoyl, CH2O-benzoyl alkyl substituted O-alkanoyl, CH2O-alkanoyl substituted phenyl, CH2O-alkenoyl substituted phenyl, CH2O-aryl, CH2O-acyl, CH2O-heterocylic, CH2O-heteroraryl, CH2O- alkenylcarbonyl, CH2O-ethanoyl, CH2O-propanoyl, CH2O-propenoyl, CH2O- butanoyl, CH2O-butenoyl, CH2O-pentanoyl, CH2O-hexenoyl, CH2O-heptanoyl, CH2O-heptenoyl, CH2O-octanoyl, CH2O-octenoyl, CH2O-nonanoyl, CH2O- nonenoyl, CH2O-decanoyl, CH2O-decenoyl, CH2O-propionyl, CH2O-2- propenoyl, CH2O-2-butenoyl, CH2O-lsobutyryl, CH2O-2-methylpropanoyl, CH2O-2-ethylbutyryl, CH2O-ethylbutanoyl, CH2O-2-ethylbutanoyl, CH2O-butyryl, CH2O-(E)-2,3-Dimethylacryloyl, CH2O-(E)-2-Methylcrotonoyl, CH2O-3-C/S- Methyl-methacryloyl, CH2O-3-Methyl-2-butenoyl, CH2O-3-Methylcrotonoyl, CH2O-4-Pentenoyl, CH2O-(2E)-2-pentenoyl, CH2O-Caproyl, CH2O-5-Hexenoyl, CH2O-Capryloyl, CH2O-Lauroyl, CH2O-Dodecanoyl, CH2O-Myristoyl, CH2O- Tetradecanoyl, CH2O-Oleoyl, CH2O-C(2-18) Acyl; wherein R3 is OH or H or absent; wherein R1 , R2, R3, R5, R8 are OH or H or absent; wherein R9, R1 1 , R12, R13, R14, and R15 are CH3; or wherein R1 , R2, R5, R8 represent OH; R3 represents OH, H or absent; R4, R10 represent CH2Oangeloyl; R9, R1 1 , R12, R13, R14, R15 represent CH3; or wherein R1 , R2, R5, R8 represent OH or O- tigloyl; R3 represents OH, H, or absent; R4, R10 represent CH2O tigloyl; R9, R1 1 , R12, R13, R14, R15 represent CH3; wherein the group attaching to the core compound selected from acetyl, angeloyl, tigloyl, senecioyl, Crotonoyl, O- 3,3-Dimethylartyloyl, Cinnamoyl, Pentenoyl, HexanoyI, benzoyl, Ethylbutyryl, alkyl, dibenzoyl, benzoyl, methylbutanoyl, methylpropanoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, alkanoyl substituted phenyl, alkenoyl substituted phenyl, aryl, acyl, heterocylic, heteroraryl, alkenylcarbonyl, ethanoyl, propanoyl, propenoyl, butanoyl, butenoyl, pentanoyl, hexenoyl, heptanoyl, heptenoyl, octanoyl, octenoyl, nonanoyl, nonenoyl, decanoyl, decenoyl, propionyl, 2-propenoyl, 2-butenoyl, Isobutyryl, 2-methylpropanoyl, 2-ethylbutyryl, ethylbutanoyl, 2-ethylbutanoyl, butyryl, (E)-2,3-Dimethylacryloyl, (E)-2- Methylcrotonoyl, 3-c/s-Methyl-methacryloyl, 3-Methyl-2-butenoyl, 3- Methylcrotonoyl, 4-Pentenoyl, (2E)-2-pentenoyl, Caproyl, 5-Hexenoyl, Capryloyl, Lauroyl, Dodecanoyl, Myristoyl, TetradecanoyI, Oleoyl, C(2-18) Acyl are interchangeable or replaceable thereof. The compound of any of claim 1 to 2, wherein R10 and at least 1 or 2 of R1 , R2, R3, R4, R5, R8, are independently attached an O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, O-3,3-Dimethylartyloyl, O-Cinnamoyl, O-Pentenoyl, O- Hexanoyl, O-benzoyl, O-Ethylbutyryl,O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O- heteroraryl, O-alkenylcarbonyl, O-alkane, O-alkene, O-sugar moiety, O-ethanoyl, O-propanoyl, O-propenoyl, O-butanoyl, O-butenoyl, O-pentanoyl, O-hexenoyl, O- heptanoyl, O-heptenoyl, O-octanoyl, O-octenoyl, O-nonanoyl, O-nonenoyl, O- decanoyl, O-decenoyl, O-propionyl, O-2-propenoyl, O-2-butenoyl, O-lsobutyryl, O-2-methylpropanoyl, O-2-ethylbutyryl, O-ethylbutanoyl, O-2-ethylbutanoyl, O- butyryl, O-(E)-2,3-Dimethylacryloyl, O-(E)-2-Methylcrotonoyl, O-3-c/s-Methyl- methacryloyl, 0-3-Methyl-2-butenoyl, O-3-Methylcrotonoyl, O-4-Pentenoyl, O- (2E)-2-pentenoyl, O-Caproyl, O-5-Hexenoyl, O-Capryloyl, O-Lauroyl, O- Dodecanoyl, O-Myristoyl, O-Tetradecanoyl, O-Oleoyl, 0-C(2-18) Acyl, CH20- angeloyl, CH2O-tigloyl, CH2O-senecioyl, CH2O-acetyl, CH2O-Crotonoyl, CH20- 3,3-Dimethylartyloyl, CH2O-Cinnamoyl, CH2O-Pentenoyl, CH2O-Hexanoyl, CH2O-benzoyl, CH2O-Ethylbutyryl, CH2O-alkyl, CH2O-dibenzoyl, CH20- benzoyl, CH2O-alkanoyl, CH2O-alkenoyl, CH20-benzoyl alkyl substituted O- alkanoyl, CH20-alkanoyl substituted phenyl, CH20-alkenoyl substituted phenyl, CH20-aryl, CH20-acyl, CH20-heterocylic, CH20-heteroraryl, CH20- alkenylcarbonyl, CH20-ethanoyl, CH20-propanoyl, CH20-propenoyl, CH20- butanoyl, CH20-butenoyl, CH20-pentanoyl, CH20-hexenoyl, CH20-heptanoyl, CH20-heptenoyl, CH20-octanoyl, CH20-octenoyl, CH20-nonanoyl, CH20- nonenoyl, CH20-decanoyl, CH20-decenoyl, CH20-propionyl, CH20-2- propenoyl, CH20-2-butenoyl, CH20-lsobutyryl, CH20-2-methylpropanoyl, CH20-2-ethylbutyryl, CH20-ethylbutanoyl, CH20-2-ethylbutanoyl, CH20-butyryl, CH20-(E)-2,3-Dimethylacryloyl, CH20-(E)-2-Methylcrotonoyl, CH20-3-C/S- Methyl-methacryloyl, CH20-3-Methyl-2-butenoyl, CH20-3-Methylcrotonoyl, CH20-4-Pentenoyl, CH20-(2E)-2-pentenoyl, CH20-Caproyl, CH20-5-Hexenoyl, CH20-Capryloyl, CH20-Lauroyl, CH20-Dodecanoyl, CH20-Myristoyl, CH20- Tetradecanoyl, CH20-Oleoyl, CH20-C(2-18) Acyl. The compound of any of claim 1 to 2, wherein R1 , R4 and R10 are independently attached an O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, 0-3,3- Dimethylartyloyl, O-Cinnamoyl, O-Pentenoyl, O-Hexanoyl, O-benzoyl, O- Ethylbutyryl,O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O- alkenylcarbonyl, O-alkane, O-alkene, O-sugar moiety, O-ethanoyl, O-propanoyl, O-propenoyl, O-butanoyl, O-butenoyl, O-pentanoyl, O-hexenoyl, O-heptanoyl, O- heptenoyl, O-octanoyl, O-octenoyl, O-nonanoyl, O-nonenoyl, O-decanoyl, O- decenoyl, O-propionyl, O-2-propenoyl, O-2-butenoyl, O-lsobutyryl, O-2- methylpropanoyl, O-2-ethylbutyryl, O-ethylbutanoyl, O-2-ethylbutanoyl, O-butyryl, O- (E)-2,3-Dimethylacryloyl, O-(E)-2-Methylcrotonoyl, O-3-c/s-Methyl- methacryloyl, O-3-Methyl-2-butenoyl, O-3-Methylcrotonoyl, O-4-Pentenoyl, O- (2E)-2-pentenoyl, O-Caproyl, O-5-Hexenoyl, O-Capryloyl, O-Lauroyl, O- Dodecanoyl, O-Myristoyl, O-Tetradecanoyl, O-Oleoyl, O-C(2-18) Acyl, CH2O- angeloyl, CH2O-tigloyl, CH2O-senecioyl, CH2O-acetyl, CH2O-Crotonoyl, CH20- 3,3-Dimethylartyloyl, CH20-Cinnamoyl, CH2O-Pentenoyl, CH2O-Hexanoyl, CH2O-benzoyl, CH2O-Ethylbutyryl, CH2O-alkyl, CH2O-dibenzoyl, CH20- benzoyl, CH2O-alkanoyl, CH2O-alkenoyl, CH20-benzoyl alkyl substituted O- alkanoyl, CH20-alkanoyl substituted phenyl, CH20-alkenoyl substituted phenyl, CH20-aryl, CH20-acyl, CH20-heterocylic, CH20-heteroraryl, CH20- alkenylcarbonyl, CH20-alkane, CH20-alkene and CH20-sugar moiety, CH20- angeloyl, CH20-tigloyl, CH20-senecioyl, CH20-acetyl, CH20-Crotonoyl, CH20- 3,3-Dimethylartyloyl, CH20-Cinnamoyl, CH20-Pentenoyl, CH20-Hexanoyl, CH20-benzoyl, CH20-Ethylbutyryl, CH3, CH20H, CH20-alkyl, CH20-dibenzoyl, CH20-benzoyl, CH20-alkanoyl, CH20-alkenoyl, CH20-benzoyl alkyl substituted 0-alkanoyl, CH2O-alkanoyl substituted phenyl, CH2O-alkenoyl substituted phenyl, CH2O-aryl, CH2O-acyl, CH2O-heterocylic, CH2O-heteroraryl, CH2O- alkenylcarbonyl, CH2O-ethanoyl, CH2O-propanoyl, CH2O-propenoyl, CH2O- butanoyl, CH2O-butenoyl, CH2O-pentanoyl, CH2O-hexenoyl, CH2O-heptanoyl, CH2O-heptenoyl, CH2O-octanoyl, CH2O-octenoyl, CH2O-nonanoyl, CH2O- nonenoyl, CH2O-decanoyl, CH2O-decenoyl, CH2O-propionyl, CH2O-2- propenoyl, CH2O-2-butenoyl, CH2O-lsobutyryl, CH2O-2-methylpropanoyl, CH2O-2-ethylbutyryl, CH2O-ethylbutanoyl, CH2O-2-ethylbutanoyl, CH2O-butyryl, CH2O-(E)-2,3-Dimethylacryloyl, CH2O-(E)-2-Methylcrotonoyl, CH2O-3-C/S- Methyl-methacryloyl, CH2O-3-Methyl-2-butenoyl, CH2O-3-Methylcrotonoyl, CH2O-4-Pentenoyl, CH2O-(2E)-2-pentenoyl, CH2O-Caproyl, CH2O-5-Hexenoyl, CH2O-Capryloyl, CH2O-Lauroyl, CH2O-Dodecanoyl, CH2O-Myristoyl, CH2O- Tetradecanoyl, CH2O-Oleoyl, CH2O-C(2-18) Acyl. The compound of any of claim 1 to 2, wherein R4 and R10 are independently attached an O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, 0-3,3- Dimethylartyloyl, O-Cinnamoyl, O-Pentenoyl, O-Hexanoyl, O-benzoyl, O- Ethylbutyryl,O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O- alkenylcarbonyl, O-alkane, O-alkene, O-sugar moiety, O-ethanoyl, O-propanoyl, O-propenoyl, O-butanoyl, O-butenoyl, O-pentanoyl, O-hexenoyl, O-heptanoyl, O- heptenoyl, O-octanoyl, O-octenoyl, O-nonanoyl, O-nonenoyl, O-decanoyl, O- decenoyl, O-propionyl, O-2-propenoyl, O-2-butenoyl, O-lsobutyryl, O-2- methylpropanoyl, O-2-ethylbutyryl, O-ethylbutanoyl, O-2-ethylbutanoyl, O-butyryl, O- (E)-2,3-Dimethylacryloyl, O-(E)-2-Methylcrotonoyl, O-3-c/s-Methyl- methacryloyl, 0-3-Methyl-2-butenoyl, O-3-Methylcrotonoyl, O-4-Pentenoyl, O- (2E)-2-pentenoyl, O-Caproyl, O-5-Hexenoyl, O-Capryloyl, O-LauroyI, O- Dodecanoyl, O-Myristoyl, O-Tetradecanoyl, O-Oleoyl, O-C(2-18) Acyl, CH2O- angeloyl, CH2O-tigloyl, CH2O-senecioyl, CH2O-acetyl, CH2O-Crotonoyl, CH2O- 3,3-Dimethylartyloyl, CH2O-Cinnamoyl, CH2O-Pentenoyl, CH2O-Hexanoyl, CH2O-benzoyl, CH2O-Ethylbutyryl, CH3, CH2OH, CH2O-alkyl, CH2O-dibenzoyl, CH2O-benzoyl, CH2O-alkanoyl, CH2O-alkenoyl, CH2O-benzoyl alkyl substituted O-alkanoyl, CH2O-alkanoyl substituted phenyl, CH2O-alkenoyl substituted phenyl, CH2O-aryl, CH2O-acyl, CH2O-heterocylic, CH2O-heteroraryl, CH2O- alkenylcarbonyl, CH2O-ethanoyl, CH2O-propanoyl, CH2O-propenoyl, CH2O- butanoyl, CH2O-butenoyl, CH2O-pentanoyl, CH2O-hexenoyl, CH2O-heptanoyl, CH2O-heptenoyl, CH2O-octanoyl, CH2O-octenoyl, CH2O-nonanoyl, CH2O- nonenoyl, CH2O-decanoyl, CH2O-decenoyl, CH2O-propionyl, CH2O-2- propenoyl, CH2O-2-butenoyl, CH2O-lsobutyryl, CH2O-2-methylpropanoyl, CH2O-2-ethylbutyryl, CH2O-ethylbutanoyl, CH2O-2-ethylbutanoyl, CH2O-butyryl, CH2O-(E)-2,3-Dimethylacryloyl, CH2O-(E)-2-Methylcrotonoyl, CH2O-3-C/S- Methyl-methacryloyl, CH2O-3-Methyl-2-butenoyl, CH2O-3-Methylcrotonoyl, CH2O-4-Pentenoyl, CH2O-(2E)-2-pentenoyl, CH2O-Caproyl, CH2O-5-Hexenoyl, CH2O-Capryloyl, CH2O-Lauroyl, CH2O-Dodecanoyl, CH2O-Myristoyl, CH2O- Tetradecanoyl, CH2O-Oleoyl, CH2O-C(2-18) Acyl. The compound of any of claim 1 to 2, wherein R10 is attached an O-angeloyl, O- tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, O-3,3-Dimethylartyloyl, O-Cinnamoyl, O-Pentenoyl, O-Hexanoyl, O-benzoyl, O-Ethylbutyryl,O-alkyl, O-dibenzoyl, O- benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O- alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O- heterocylic, O-heteroraryl, O-alkenylcarbonyl, O-alkane, O-alkene, O-sugar moiety, O-ethanoyl, O-propanoyl, O-propenoyl, O-butanoyl, O-butenoyl, O- pentanoyl, O-hexenoyl, O-heptanoyl, O-heptenoyl, O-octanoyl, O-octenoyl, O- nonanoyl, O-nonenoyl, O-decanoyl, O-decenoyl, O-propionyl, O-2-propenoyl, O- 2-butenoyl, O-lsobutyryl, O-2-methylpropanoyl, O-2-ethylbutyryl, O-ethylbutanoyl, O-2-ethylbutanoyl, O-butyryl, O- (E)-2,3-Dimethylacryloyl, O-(E)-2- Methylcrotonoyl, O-3-c/s-Methyl-methacryloyl, O-3-Methyl-2-butenoyl, O-3- Methylcrotonoyl, O-4-Pentenoyl, O-(2E)-2-pentenoyl, O-Caproyl, O-5-Hexenoyl, O-Capryloyl, O-Lauroyl, O-Dodecanoyl, O-Myristoyl, O-Tetradecanoyl, O-Oleoyl, 0-C(2-18) Acyl, CH2O-angeloyl, CH2O-tigloyl, CH2O-senecioyl, CH2O-acetyl, CH2O-Crotonoyl, CH2O-3,3-Dimethylartyloyl, CH2O-Cinnamoyl, CH20- Pentenoyl, CH2O-Hexanoyl, CH2O-benzoyl, CH2O-Ethylbutyryl, CH3, CH20H, CH2O-alkyl, CH2O-dibenzoyl, CH2O-benzoyl, CH2O-alkanoyl, CH2O-alkenoyl, CH20-benzoyl alkyl substituted 0-alkanoyl, CH2O-alkanoyl substituted phenyl, CH2O-alkenoyl substituted phenyl, CH2O-aryl, CH2O-acyl, CH2O-heterocylic, CH2O-heteroraryl, CH2O-alkenylcarbonyl, CH2O-ethanoyl, CH2O-propanoyl, CH2O-propenoyl, CH2O-butanoyl, CH2O-butenoyl, CH2O-pentanoyl, CH2O- hexenoyl, CH2O-heptanoyl, CH2O-heptenoyl, CH2O-octanoyl, CH2O-octenoyl, CH2O-nonanoyl, CH2O-nonenoyl, CH2O-decanoyl, CH2O-decenoyl, CH2O- propionyl, CH2O-2-propenoyl, CH2O-2-butenoyl, CH2O-lsobutyryl, CH2O-2- methylpropanoyl, CH2O-2-ethylbutyryl, CH2O-ethylbutanoyl, CH2O-2- ethylbutanoyl, CH2O-butyryl, CH2O-(E)-2,3-Dimethylacryloyl, CH2O-(E)-2- Methylcrotonoyl, CH2O-3-c/s-Methyl-methacryloyl, CH2O-3-Methyl-2-butenoyl, CH2O-3-Methylcrotonoyl, CH2O-4-Pentenoyl, CH2O-(2E)-2-pentenoyl, CH2O- Caproyl, CH2O-5-Hexenoyl, CH2O-Capryloyl, CH2O-Lauroyl, CH2O- Dodecanoyl, CH2O-Myristoyl, CH2O-Tetradecanoyl, CH2O-Oleoyl, CH2O-C(2- 18) Acyl. The compound of any of claim 1 to 2, wherein R4 and R10 are independently attached an CH2O-angeloyl, CH2O-tigloyl, CH2O-senecioyl, CH2O-acetyl, CH2O-Crotonoyl, CH2O-3,3-Dimethylartyloyl, CH2O-Cinnamoyl, CH2O- Pentenoyl, CH2O-Hexanoyl, CH2O-benzoyl, CH2O-Ethylbutyryl, CH3, CH2OH, CH2O-alkyl, CH2O-dibenzoyl, CH2O-benzoyl, CH2O-alkanoyl, CH2O-alkenoyl, CH2O-benzoyl alkyl substituted O-alkanoyl, CH2O-alkanoyl substituted phenyl, CH2O-alkenoyl substituted phenyl, CH2O-aryl, CH2O-acyl, CH2O-heterocylic, CH2O-heteroraryl, CH2O-alkenylcarbonyl, CH2O-ethanoyl, CH2O-propanoyl, CH2O-propenoyl, CH2O-butanoyl, CH2O-butenoyl, CH2O-pentanoyl, CH2O- hexenoyl, CH2O-heptanoyl, CH2O-heptenoyl, CH2O-octanoyl, CH2O-octenoyl, CH2O-nonanoyl, CH2O-nonenoyl, CH2O-decanoyl, CH2O-decenoyl, CH2O- propionyl, CH2O-2-propenoyl, CH2O-2-butenoyl, CH2O-lsobutyryl, CH2O-2- methylpropanoyl, CH2O-2-ethylbutyryl, CH2O-ethylbutanoyl, CH2O-2- ethylbutanoyl, CH2O-butyryl, CH2O-(E)-2,3-Dimethylacryloyl, CH2O-(E)-2- Methylcrotonoyl, CH2O-3-c/'s-Methyl-methacryloyl, CH2O-3-Methyl-2-butenoyl, CH2O-3-Methylcrotonoyl, CH2O-4-Pentenoyl, CH2O-(2E)-2-pentenoyl, CH2O- Caproyl, CH2O-5-Hexenoyl, CH2O-Capryloyl, CH2O-Lauroyl, CH2O- Dodecanoyl, CH2O-Myristoyl, CH2O-Tetradecanoyl, CH2O-Oleoyl, CH20-C(2- 18) Acyl; wherein R1 , R2, R3, R5, R8 are OH or H or absent; wherein R9, R1 1 , R12, R13, R14, and R15 are CH3. The compound of any of claim 1 to 2, wherein any 2 of R1 , R2, R3, R4, R5, R8, are independently attached an O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O- Crotonoyl, 0-3,3-Dimethylartyloyl, O-Cinnamoyl, O-Pentenoyl, O-Hexanoyl, O- benzoyl, 0-Ethylbutyryl,0-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O- alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O- alkenylcarbonyl, O-alkane, O-alkene, O-sugar moiety, O-ethanoyl, O-propanoyl, O-propenoyl, O-butanoyl, O-butenoyl, O-pentanoyl, O-hexenoyl, O-heptanoyl, O- heptenoyl, O-octanoyl, O-octenoyl, O-nonanoyl, O-nonenoyl, O-decanoyl, O- decenoyl, O-propionyl, O-2-propenoyl, O-2-butenoyl, O-lsobutyryl, 0-2- methylpropanoyl, O-2-ethylbutyryl, O-ethylbutanoyl, O-2-ethylbutanoyl, O-butyryl, O- (E)-2,3-Dimethylacryloyl, O-(E)-2-Methylcrotonoyl, O-3-c/s-Methyl- methacryloyl, O-3-Methyl-2-butenoyl, O-3-Methylcrotonoyl, O-4-Pentenoyl, O- (2E)-2-pentenoyl, O-Caproyl, O-5-Hexenoyl, O-Capryloyl, O-Lauroyl, O- Dodecanoyl, O-Myristoyl, O-Tetradecanoyl, O-Oleoyl, O-C(2-18) Acyl, CH2O- angeloyl, CH2O-tigloyl, CH2O-senecioyl, CH2O-acetyl, CH2O-Crotonoyl, CH2O- 3,3-Dimethylartyloyl, CH2O-Cinnamoyl, CH2O-Pentenoyl, CH2O-Hexanoyl, CH2O-benzoyl, CH2O-Ethylbutyryl, CH3, CH2OH, CH2O-alkyl, CH2O-dibenzoyl, CH2O-benzoyl, CH2O-alkanoyl, CH2O-alkenoyl, CH2O-benzoyl alkyl substituted O-alkanoyl, CH2O-alkanoyl substituted phenyl, CH2O-alkenoyl substituted phenyl, CH2O-aryl, CH2O-acyl, CH2O-heterocylic, CH2O-heteroraryl, CH2O- alkenylcarbonyl, CH2O-ethanoyl, CH2O-propanoyl, CH2O-propenoyl, CH2O- butanoyl, CH2O-butenoyl, CH2O-pentanoyl, CH2O-hexenoyl, CH2O-heptanoyl, CH2O-heptenoyl, CH2O-octanoyl, CH2O-octenoyl, CH2O-nonanoyl, CH2O- nonenoyl, CH2O-decanoyl, CH2O-decenoyl, CH2O-propionyl, CH2O-2- propenoyl, CH2O-2-butenoyl, CH2O-lsobutyryl, CH2O-2-methylpropanoyl, CH2O-2-ethylbutyryl, CH2O-ethylbutanoyl, CH2O-2-ethylbutanoyl, CH2O-butyryl, CH2O-(E)-2,3-Dimethylacryloyl, CH2O-(E)-2-Methylcrotonoyl, CH2O-3-C/S- Methyl-methacryloyl, CH2O-3-Methyl-2-butenoyl, CH2O-3-Methylcrotonoyl, CH2O-4-Pentenoyl, CH2O-(2E)-2-pentenoyl, CH2O-Caproyl, CH2O-5-Hexenoyl, CH2O-Capryloyl, CH2O-Lauroyl, CH2O-Dodecanoyl, CH2O-Myristoyl, CH2O- Tetradecanoyl, CH2O-Oleoyl, CH2O-C(2-18) Acyl. The compound of any of claim 1 to 2, wherein the compound is selected from the following: a) An isolated, purified or synthesized compound having structure: , or chemical name: 24,28-O-Tigloyl- 3β,16α, 21 β, 22α, 24β, 28-hexahydroxyolean-12-ene b) An isolated, purified or synthesized compound having structure: or chemica| name : 24-0-Tigloyl-3 ,16a, 21 β, 22a, 24β, 28-hexahydroxyolean-12-ene pound having structure: or Chemjca| name: 22,28-O-Tigloyl- 3β,16α, 21 β, 22α, 24β, 28-hexahydroxyolean-12-ene pound having structure: or chemical name: 21 ,24,28-0- Tigloyl-3 ,16a, 21 β, 22a, 24β, 28-hexahydroxyolean-12-ene e) An isolated, purified or synthesized compound having structure: Qr Chemjca| name: 22,24,28-0- Tigloyl-3 ,16a, 21 β, 22a, 24β, 28-hexahydroxyolean-12-ene aving structure: chemical name: 3,21 ,28-0- Tigloyl-3 ,16a, 21 β, 22a, 24β, 28-hexahydroxyolean-12-ene g) An isolated, purified or synthesized compound having structure: , or chemical name: 21 ,24-O-Tigloyl- 3β,16α, 21 β, 22α, 24β, 28-hexahydroxyolean-12-ene 10. The composition comprises compound of any of claim 1 to 9, further comprising a pharmaceutically acceptable carrier or diluent. 1 1 . The compound of any of claim 1 to 9, wherein the compound for treating cancer, inhibiting cancer growth, inhibiting cancer invasion, inhibiting cancer metastasis, modulating cell adhesion, modulating cell attachment, wherein the cancer is selected from the group of breast cancer, leukocytic cancer, liver cancer, ovarian cancer, bladder cancer, prostatic cancer, skin cancer, bone cancer, brain cancer, leukemia cancer, lung cancer, colon cancer, CNS cancer, melanoma cancer, renal cancer, cervical cancer, esophageal cancer, testicular cancer, spleenic cancer, kidney cancer, lymphhatic cancer, pancreatic cancer, stomach cancer and thyroid cancer; wherein the cells is selected from the group of breast cell, leukocytic cell, liver cell, ovarian cell, bladder cell, prostatic cell, skin cell, bone cell, brain cell, leukemia cell, lung cell, colon cell, CNS cell, melanoma cell, renal cell, cervical cell, esophageal cell, testicular cell, spleenic cell, kidney cell, lymphhatic cell, pancreatic cell, stomach cell and thyroid cell. 12. The compound of any of claim 1 to 9, wherein the compound for treating cancers, inhibition of cancer growth, cancer invasion, cells invasion, cancer cell invasion; cell adhesion, cell attachment, cell circulating; for inhibiting viruses; for preventing cerebral aging; for improving memory; improving cerebral functions; for curing enuresis, frequent micturition, urinary incontinence; dementia, Alzheimer's disease, autism, brain trauma, Parkinson's disease or other neurodegenerative diseases caused by cerebral dysfunctions; for treating arthritis, rheumatism, poor circulation, arteriosclerosis, Raynaud's syndrome, angina pectoris, cardiac disorder, coronary heart disease, headache, dizziness, kidney disorder; cerebrovascular diseasea; inhibiting NF-kappa B activation; for treating brain edema, severe acute respiratory syndrome, respiratory viral diseases, chronic venous insufficiency, hypertension, chronic venous disease, oedema, inflammation, hemonhoids, peripheral edema formation, varicose vein disease, flu, post traumatic edema and postoperative swelling; for inhibiting blood clots, for inhibiting ethanol absorption; for lowering blood sugar; for regulating adrenocorticotropin and corticosterone levels. This invention provides a composition for Anti-MS, anti-aneurysm, anti-asthmatic, anti-oedematous, antiinflammatory, anti-bradykinic, anti-capillarihemorrhagic, anti-cephalagic, anti- cervicobrachialgic, anti-eclamptic, anti-edemic, anti-encaphalitic, anti-epiglottitic, anti-exudative, anti-flu, anti-fracture, anti-gingivitic, anti-hematomic, anti-herpetic, anti-histaminic, anti-hydrathritic, anti-meningitic, antioxidant, anti-periodontic, anti-phlebitic, anti-pleuritic, anti-raucedo, anti-rhinitic, anti-tonsilitic, anti-ulcer, anti-varicose, anti-vertiginous, cancerostatic, corticosterogenic, diuretic, fungicide, hemolytic, hyaluronidase inhibitor, lymphagogue, natriuretic, pesticide, pituitary stimulant, thymolytic, vasoprotective, inhibiting leishmaniases, modulating adhesion or angiogenesis of cells, anti-parasitic; increase the expression of the genes: ANGPT2, DDIT3, LIF and NFKB1 Z, and manufacturing an adjuvant composition and venotonic treatment. 3. The compound of any of claim 1 to 9, wherein the compound for anti-adhesion therapy. 4. A composition comprising an effective amount of compound of any of claim 1 to 9 as a medicament. 5. The compound of any of claim 1 to 9, wherein the compound can be obtained with the method: 1 . Dissolving core compound or triterpenes, hydroxylated triterpenes core in pyridine, 2. Adding acyl chloride, 3. The mixture is stirred for length of time including 5 sec, 10 sec, 20 sec, 30 sec, 40sec,1 min, 2 min, 5 min, 10 min, 30 min, 1 hr, 2 hr, 18 hr, 2 days or 3 days at different temperature, 4. At the end of reaction, an aqueous solution of acid or base, or water is added to the reaction mixture, 5. The solution is then extracted of ethyl acetate and ethyl acetate is removed by evaporation and and lyophilization, 6. Dissolving the reaction product in acetonitrile with Trifluoroacetic acid or DMSO, 7. Testing the reaction product of mixtures and individual fractions with MTT cytotoxic assay, 8. Selecting the HPLC fractions for isolation is according to the cytotoxic activity of the reaction product obtained at a specific reaction time, 9. Purifiing the active esterification products with HPLC, 10. Collecting the products, 1 1 . Testing the products. 6. The compound of claim 15, wherein the core compound is terpene, isoprene, or triterpene core; wherein the core compound is hydroxylated; wherein the core compound was dissolved in pyridine; wherein the acyl chloride including Tigloyl chloride, angeloyl chloride, Acetyl chloride, Crotonoyl chloride, 3,3- Dimethylartyloyl chloride, senecioyl chloride, Cinnamoyl chloride, Pentenoyl chloride, Hexanoyl chloride, benzoyl chloride and Ethylbutyryl chloride; wherein the reaction time for the mixture is stirred for 5 sec, 1 min, 2 min, 5 min, 10 min, 30 min, 1 hr, 2 hr, 18 hr, 2 days or 3 days; wherein the temperature is 0C, 25C, 50 or 75C temperature; wherein the acid including HCI or the base is a weak base including NaHC03 is added to the reaction mixture; wherein the solution is then extracted 3 times with ethyl acetate and lyophilization; wherein the reaction product is dissolved in 80% acetonitrile - 0.005% Trifluoroacetic acid or DMSO; wherein selecting the HPLC fractions for isolation is according to the cytotoxic activity of the reaction product obtained at a reaction time of 5 sec, 1 min, 2 min, 5 min, 10 min, 30 min, 1 hr, 2 hr, 18 hr, 2 days or 3 days. 7. The compound of claim 1 , wherein the said compound is present in a concentration of 0.01 ug/ml to 40ug/ml, or wherein said compound is present in a concentration of 0.01 ug/ml to 30ug/ml, or wherein said compound is present in a concentration of 0.01 ug/ml to 10ug/ml, or wherein said compound is present in a concentration of 0.01 ug/ml to 5ug/ml, or wherein said compound is present in a concentration of 5 ug/ml to 10ug/ml, or wherein said compound is present in a concentration of 0.1 ug/ml to 5ug/ml, or wherein said compound is present in a concentration of 0.1 ug/ml to 7.5ug/ml, or wherein said compound is present in a concentration of 0.1 ug/ml to 10ug/ml, or wherein said compound is present in a concentration of 0.1 ug/ml to 15ug/ml, or wherein said compound is present in a concentration of 0.1 ug/ml to 20ug/ml, or wherein said compound is present in a concentration of 0.1 ug/ml to 30ug/ml, or wherein said compound is present in a concentration of 1 ug/ml to 5ug/ml, or wherein said compound is present in a concentration of 1 ug/ml to 7.5ug/ml, or wherein said compound is present in a concentration of 1 ug/ml to 10ug/ml, or wherein said compound is present in a concentration of 1 ug/ml to 15ug/ml, or wherein said compound is present in a concentration of 1 ug/ml to 20ug/ml, or wherein said compound is present in a concentration of 1 ug/ml to 30ug/ml, or wherein said compound is present in a concentration of 3 ug/ml to 5ug/ml, or wherein said compound is present in a concentration of 3 ug/ml to 7.5ug/ml, or wherein said compound is present in a concentration of 3 ug/ml to 10ug/ml, or wherein said compound is present in a concentration of 3 ug/ml to 15ug/ml, or wherein said compound is present in a concentration of 3 ug/ml to 20ug/ml, or wherein said compound is present in a concentration of 3 ug/ml to 30ug/ml; or present in a concentration of 4 ug/ml to 5ug/ml, or wherein said compound is present in a concentration of 4 ug/ml to 7.5ug/ml, or wherein said compound is present in a concentration of 4 ug/ml to 10ug/ml, or wherein said compound is present in a concentration of 4 ug/ml to 15ug/ml, or wherein said compound is present in a concentration of 4 ug/ml to 20ug/ml, or wherein said compound is present in a concentration of 4 ug/ml to 30ug/ml, or present in a concentration of 5 ug/ml to 8ug/ml, or wherein said compound is present in a concentration of 5 ug/ml to 9ug/ml, or wherein said compound is present in a concentration of 5 ug/ml to 10ug/ml, or wherein said compound is present in a concentration of 5 ug/ml to 15ug/ml, or wherein said compound is present in a concentration of 5 ug/ml to 20ug/ml, or wherein said compound is present in a concentration of 5 ug/ml to 30ug/ml, or present in a concentration of 7 ug/ml to 8ug/ml, or wherein said compound is present in a concentration of 7 ug/ml to 9ug/ml, or wherein said compound is present in a concentration of 7 ug/ml to 10ug/ml, or wherein said compound is present in a concentration of 7 ug/ml to 15ug/ml, or wherein said compound is present in a concentration of 7 ug/ml to 20ug/ml, or wherein said compound is present in a concentration of 7 ug/ml to 30ug/ml; or wherein administration is by intravenous drip: 0.003-0.03mg/kg body weight of compound dissolved in 250ml of 10% glucose solution or in 250ml of 0.9% NaCI solution, or by intravenous injection: 0.003-0.03mg/kg body weight per day of compound dissolved in 10-20ml of 10% glucose solution or of 0.9% NaCI solution, or 0.01 -0.03mg/kg body weight of compound dissolved in 250ml of 10% glucose solution or in 250ml of 0.9% NaCI solution, or by intravenous injection: 0.01 -0.03mg/kg body weight per day of compound dissolved in 10-20ml of 10% glucose solution or of 0.9% NaCI solution, or 0.01 -0.05mg/kg body weight of compound dissolved in 250ml of 10% glucose solution or in 250ml of 0.9% NaCI solution, or by intravenous injection: 0.01 - 0.05.g/kg body weight per day of compound dissolved in 10-20ml of 10% glucose solution or of 0.9% NaCI solution. 8. A method for inhibiting cancer growth or treating cancer comprising contacting said cells or administering to said subject with an effective amount of a compound, wherein the compound is selected from claim 1 . 9. The method of synthesizing of compound of claim 1 , wherein the method comprising steps of: 1 . Dissolving 40 mg of triterpene core in 1 ml pyridine in a 50 ml tube, 2. Adding 0.2 ml of acyl chloride comprising Tigloyl chloride and angeloyl chloride, 3. Stirring the mixture for 1 , 2 or 3 days at room temperature, 4. Adding 3 ml of NaHC03 is slowly added to the reaction mixture, 5. Extracting the solution 3 times with 10 ml of ethyl acetate, 6. Evaporating the solution under vacuum and at 45C and lyophilization, 7. Dissolving the reaction product in 80% acetonitrile - 0.005% Trifluoroacetic acid, 8. Selecting the HPLC fractions for isolation according to the cytotoxic activity of times studies and the change of peaks, 9. Purifing the active esterification products with HPLC. 0. A method of determining cell invasive with compound selected from claim 1 : 1 . Determinating the non-cytotoxic concentrations of individual compound selected from claim 1 that is used for the invasion assay, 2. Exposeing cancer cells to different drug concentrations for 1 , and 2days, wherein the cancers are selected from breast cancer, leukocytic cancer, liver cancer, ovarian cancer, bladder cancer, prostatic cancer, skin cancer, bone cancer, brain cancer, leukemia cancer, lung cancer, colon cancer, CNS cancer, melanoma cancer, renal cancer, cervical cancer, esophageal cancer, testicular cancer, spleenic cancer, kidney cancer, lymphatic cancer, pancreatic cancer, stomach cancer and thyroid cancer. The growth of cells was measured by MTT assay, 3. Presenting the optical density (O.D.) of the MTT product (formazan) reflecting cell growth in cells after drug-treatment of day 0, 1 and 2 were measured and plotted (growth curves), 4. Determinating and selecting the concentrations of drug that inhibit 15% cell- growth or less (i.e. 85% of control or above) as compared to the no-drug control (DMSO) are considered non-cytotoxic concentrations, 5. Seeding Cells (5-1 OK per well) in a 96-wells plate overnight, 6. Replaceing Culture medium with fresh medium containing different drugs, 7. Selecting the drug concentrations depends on the non-cytotoxic concentrations, 8. Using DMSO as the no-drug control, 9. Cells were incubated for 1 and 2 days, 10. Measuring Cell growth with MTT assay after 0, 1 or 2 days of incubation, 1 1 . Incubating the cell cultures with MTT (3-[4,5-Dimethylthiazol-2-yl]-2,5- diphenyl-tetrazolium bromide) (0.5 mg/ml) for 1 h and the formazan formed was dissolved with DMSO. The optical density (O.D.) of formazan at 490 nm was measured, 12. Plotting the O.D. of samples against the time (days) of incubation (Growth curves), 13. Determinating the concentration of drugs that has no effect on cell growth or reduces 15% or less of control, after 1 day incubation are listed in the following table. These drug concentrations (ug/ml) (or less) are considered as non-cytotoxic are then employed in the invasion assay, 14. Filling both upper and lower chambers with specific culture medium (according to the requirement of individual cell lines) also containing 10% FBS, wherein an upper and a lower chamber which is separated with a membrane containing a thin layer of reconstituted basement membrane materials (BD BioCoatTM MatrigelTM invasion Chamber system ), 15. Placing samples to both upper and lower chambers, 16. Employing non-cytotoxic drug concentration (determined by the growth curves) in this assay. DMSO was used as the non-drug control, 17. Applying equal numbers (usually 20K per well) of cells into the upper chamber, 18. Counting invasive cells that passed through the membrane from the upper chamber to the lower chamber and attached at the bottom of membrane after 24 hours of incubation which were fixed (with methanol), then stained (with 1 % Toluidine Blue), and air dry, 19. Calculating the percentage of invasive cells (as compared to DMSO control), 20. Summarising the percentage of cells (compared to control) that passed the membrane at certain drug concentration and is listed in table. A method of delivering the compounds as medicament with a liposomes or nanoparticles capsules as a carrier, wherein the size of liposomes or nanoparticles capsules is less than 200 nm or 100-200 nm or 50-100 nm or 5-50 nm, wherein the medicament is included but not limited for treating cancer, inhibiting cancer growth, inhibiting cancer invasion, inhibiting cancer metastasis, modulating cell adhesion, modulating cell attachment, or anti adhesion therapy wherein the compound is selected from claim 1 . |
OTHER DISEASES
This application claims priority of US serial No. 13/259,480, filed July 15, 2011 and International Application No. PCT/US201 1/044233, filed July 15, 201 1 , which is a continuation-in-part of International App'l No. PCT/US2010/0042240, filed July 16, 2010 and U.S. Serial No 12/856,322, filed August 13, 2010. This application also claims priority of U.S. Serial No. 12/541 ,713, filed August 14, 2009 and claims benefit of U.S. Serial No. 61/226,043, filed July 16, 2009. This application claims priority of International App'l No. PCT/US2009/34115, filed February 13, 2009, This application claims benefit of U.S. Serial No. 61/038,277 filed March 20, 2008, U.S. Serial No. 61/054,308, filed May 19, 2008, and claims priority of International App'l No. PCT/US2008/002086, filed February 15, 2008, International App'l No. PCT/US2007/077273, filed August 30, 2007, U.S. Serial No. 60/890,380, filed February 16, 2007, U.S. No. 60/947,705, filed July 3, 2007, and U.S. Serial No. 1 1/683,198, filed March 7, 2007, which claims benefit of U.S. Serial No. 60/795,417, filed April 27, 2006, U.S. Serial No. 60/841 ,727, filed September 1 , 2006, U.S. Serial No. 60/890,380, filed on February 16, 2007, and International Application No. PCT/US2006/016158, filed April 27, 2006, which claims the benefit of the priority of the following applications: (1 ) U.S. Serial Nos. 11/289142, filed November 28, 2005, and 1 1/267,523, filed November 4, 2005; (2) International Application No. PCT/US05/31900, filed September 7, 2005 (which claims the priority of U.S. Serial Nos. 60/617,379, filed October 8, 2004, 60/613,811 , filed September 27, 2004, and 60/607,858, filed September 7, 2004); (3) U.S. Serial No. 1 1/131 ,551 , filed May 17, 2005; and (4) U.S. Serial No. 1 1/117,760, filed April 27, 2005. This application also claims priority of U.S. Serial No. 1 1/412,659, filed April 27, 2006, U.S. Serial No. 10/906,303, filed February 14, 2005, and U.S. Serial No. 12/344,682, filed December 29, 2008. The contents of these preceding applications are hereby incorporated in their entireties by reference into this application. FIELD OF THE INVENTION
This invention provides methods of synthesing new compounds for pharmaceutical uses.
BACKGROUND OF THE INVENTION
This invention provides methods of synthesing new compounds for pharmaceutical uses. This invention provides methods, compounds and compositions for treating cancer, inhibiting cancer invasion, cell invasion, or cancer cell invasion, wherein the cancers comprise breast, leukocytic, liver, ovarian, bladder, prostatic, skin, bone, brain, leukemia, lung, colon, CNS, melanoma, renal, cervical, esophageal, testicular, spleenic, kidney, lymphatic, pancreatic, stomach and thyroid cancers.
SUMMARY OF THE INVENTION
This invention provides methods of synthesizing new compounds for pharmaceutical uses. This invention provides compounds, compositions, and methods for treating cancer, inhibiting cancer invasion, cell invasion, macromolecular invasion, cancer cell invasion, and metastasis. This invention provides a use of compounds, compositions, for manufacturing medicament for treating cancer, inhibiting cancer invasion, macromolecular invasion, virus invasion and metastasis. This invention provides compounds for use as mediator or inhibitor of adhesion protein or angiopoietin, This invention provides compounds for use in a method of modulating attachment or adhesion of cells or angiogenesis, by modulating or inhibiting adhesion protein macromolecules, or angiopoietin, The compounds comprise the structures selected from the formulae in the present application, wherein the compounds are synthesized or isolated, wherein the compounds comprise the saponins, triterpenes, pentacyclic triterpenes, and compounds selected from formulae in the present application, wherein the cancers comprise breast, leukocytic, liver, ovarian, bladder, prostatic, skin, bone, brain, leukemia, lung, colon, CNS, melanoma, renal, cervical, esophageal, testicular, spleenic, kidney, lymphatic, pancreatic, stomach and thyroid cancers. This invention provides compounds for use as a mediator for cell circulating, cell moving cell homing and inflammatory diseases.
DETAILED DESCRIPTION OF THE FIGURES
Figure 1. HPLC profiles of esterification products of E4A with Tigloyl chloride (A) from different times of esterification reaction. Reaction products obtained from each time of reaction (5 sec, 1 min, 2 min, 5 min, and 10 min) were fractionated by HPLC. The profile is plotted according to HPLC elution time and optical density of fractions. Reaction was performed at Room temperature (Top row) and 0 C (bottom row).
Figure 2. HPLC profiles of esterification products of E4A with 3,3-dimethylacryloly chloride (B) from different times of esterification reaction. Reaction products obtained from each time of reaction (5 sec, 1 min, 2 min, 5 min, and 10 min) were fractionated by HPLC. The profile is plotted according to HPLC elution time and optical density of fractions. Reaction was performed at Room temperature (Top row) and 0 C (bottom row). Figure 3. TT cytotoxic activity of times study at room temperature, A: E4A-Tigloyl(A); B: E4A- 3,3-dimethylacryloly(B); C: E4A-4-pentenoyl(C).
Figure 4. MTT cytotoxic activity of times study at 0C, A: E4A-TigIoyl(A); B: E4A-3.3- dimethylacryloly(B); C: E4A-4-pentenoyl(C).
Figure 5. MTT cytotoxic activity of times study, A: E4A-cinnamoyl(J); B: E4A- hexanoyl(D); C: E4A-2-ethylbutyryl(E); and D, controls: Tig control is tigloyl chloride without E4A; AC control is acetyl chloride without E4A; H is acetyl chloride with E4A reaction 1 min.
Figure 6. MTT cytotoxic activity of times study, A: E4A-acetyl(H); B: E4A-crotonoyl(l) Figure 7. HPLC profiles of E4A-Tig in 1 min and 2 hours
Figure 8. MTT cytotoxic activity of times study for E4A-Tig. Results: E4A-Tigs from reaction of 5 sec to 1 min are most active. Activity decrease after 1 min of reaction. Minimum to no activity was obtained at 10 minutes or longer.
Figure 9. Results of HPLC profiles of E4A-Tigs : E4A, E4A-ASAP (5 sec), E4A-1 min, E4A-2min, E4A-5min, E4A-10min, E4A-30min.
Figure 10. Results of Activity order: M, N, O, P, Q, R, S, T, E4A; M = E4A has no activity.
Figure 11. (A) The IC50 of Tig-S in KB cells is about 4 ug/ml; and the corresponding IC50 in ES2 cells is less than 1 ug/ml; (B) The IC50 of Tig-S in ES2 cells, MTT assay with low doses of Tig-S, the IC50 of Tig-S in ES2 cells is approximately equal to 0.1 ug/ml
Figure 12. (A) Results: Swiss3T3 cells are mouse normal fibroblast which were used in this experiment to compare with ES2 (human ovarian cancer) in Tig-R cytotoxicity determination. The preliminary results indicate that the IC50 of Tig-R in SW3T3 cells is above 20 ug/ml while the corresponding IC50 in ES2 cells is about 2.8 ug/ml. (B) Effect of Tig-R on Normal human lung fibroblast (WI38). Results: The IC50 of Tig-R in normal human fibroblast cells (WI38) is about 10-15 ug/ml. This IC50 value is 3 times higher than those in ES2 (3 ug/ml). DETAILED DESCRIPTION OF THE INVENTION
This invention provides a method of synthesising new active compounds for pharmaceutical uses. This invention provides an anti adhesion therapy which uses the compound as a mediator or inhibitor of adhesion proteins and angiopoietins. It inhibits excessive adhesion and inhibits cell viral and macromolecular attachment. It modulates angiogenesis. The compounds also use as mediator of cell viral and macromolecular adhesion receptor(s). This invention provides compounds or a composition comprising the compounds provided in the invention for treating cancers; for inhibiting cancer growth, for inhibiting viruses; for preventing cerebral aging; for improving memory; improving cerebral functions; for curing enuresis, frequent micturition, urinary incontinence; neurodegenerative diseases, dementia, Alzheimer's disease, autism, brain trauma, Parkinson's disease or other diseases caused by cerebral dysfunctions; for treating arthritis, rheumatism, poor circulation, arteriosclerosis, Raynaud's syndrome, angina pectoris, cardiac disorder, coronary heart disease, headache, dizziness, kidney disorder; cerebrovascular diseasea; inhibiting NF-kappa B activation; for treating brain edema, severe acute respiratory syndrome, respiratory viral diseases, chronic venous insufficiency, hypertension, chronic venous disease, oedema, inflammation, hemonhoids, peripheral edema formation, varicose vein disease, flu, post traumatic edema and postoperative swelling; for inhibiting blood clots, for inhibiting ethanol absorption; for lowering blood sugar; for regulating adrenocorticotropin and corticosterone levels. This invention provides a composition for Anti-MS, anti-aneurysm, anti-asthmatic, anti-oedematous, anti-inflammatory, anti-bradykinic, anti- capillarihemorrhagic, anti-cephalagic, anti-cervicobrachialgic, anti-eclamptic, anti- edemic, anti-encaphalitic, anti-epiglottitic, anti-exudative, anti-flu, anti-fracture, anti- gingivitic, anti-hematomic, anti-herpetic, anti-histaminic, anti-hydrathritic, anti-meningitic, antioxidant, anti-periodontic, anti-phlebitic, anti-pleuritic, anti-raucedo, anti-rhinitic, anti- tonsilitic, anti-ulcer, anti-varicose, anti-vertiginous, cancerostatic, corticosterogenic, diuretic, fungicide, hemolytic, hyaluronidase inhibitor, lymphagogue, natriuretic, pesticide, pituitary stimulant, thymolytic, vasoprotective, inhibiting leishmaniases, modulating adhesion or angiogenesis of cells, anti-parasitic; increase the expression of the genes: ANGPT2, DDIT3, LIF and NFKB1Z, and manufacturing an adjuvant composition and venotonic treatment.
This invention provides compounds, compositions and methods for treating cancer diseases, inhibiting cancer invasion, for inhibiting cancer growth or for inhibiting cancer metastasis, wherein the compounds comprise the structures selected from the formulae of the present application, wherein the compounds can be synthesized or isolated, wherein the compounds comprise the triterpenes, pentacyclic triterpenes, saponins, and compounds selected from formulae in this application, wherein the cancers comprise breast cancer, leukocytic cancer, liver cancer, ovarian cancer, bladder cancer, prostatic cancer, skin cancer, bone cancer, brain cancer, leukemia cancer, lung cancer, colon cancer, CNS cancer, melanoma cancer, renal cancer, cervical cancer, esophageal cancer, testicular cancer, spleenic cancer, kidney cancer, lymphhatic cancer, pancreatic cancer, stomach cancer and thyroid cancer; wherein the cells comprise breast cell, leukocytic cell, liver cell, ovarian cell, bladder cell, prostatic cell, skin cell, bone cell, brain cell, leukemia cell, lung cell, colon cell, CNS cell, melanoma cell, renal cell, cervical cell, esophageal cell, testicular cell, spleenic cell, kidney cell, lymphhatic cell, pancreatic cell, stomach cell and thyroid cell.
This invention shows that the presence of group selected from acetyl, angeloyl, tigloyl, senecioyl, Crotonoyl, 3,3-Dimethylartyloyl, Cinnamoyl, Pentenoyl, Hexanoyl, benzoyl, Ethylbutyryl, alkyl, dibenzoyl, benzoyl, methylbutanoyl, methylpropanoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, alkanoyl substituted phenyl, alkenoyl substituted phenyl, aryl, acyl, heterocylic, heteroraryl, alkenylcarbonyl, ethanoyl, propanoyl, propenoyl, butanoyl, butenoyl, pentanoyl, hexenoyl, heptanoyl, heptenoyl, octanoyl, octenoyl, nonanoyl, nonenoyl, decanoyl, decenoyl, propionyl, 2-propenoyl, 2- butenoyl, Isobutyryl, 2-methylpropanoyl, 2-ethylbutyryl, ethylbutanoyl, 2-ethylbutanoyl, butyryl, (E)-2,3-Dimethylacryloyl, (E)-2-Methylcrotonoyl, 3-c/s-Methyl-methacryloyl, 3- Methyl-2-butenoyl, 3-Methylcrotonoyl, 4-Pentenoyl, (2E)-2-pentenoyl, Caproyl, 5- Hexenoyl, Capryloyl, Lauroyl, Dodecanoyl, Myristoyl, Tetradecanoyl, Oleoyl, C(2-18) Acyl , or sugar moiety substituted with acetyl, angeloyl, tigloyl, senecioyl, Crotonoyl, 3,3- Dimethylartyloyl, Cinnamoyl, Pentenoyl, Hexanoyl, benzoyl, Ethylbutyryl, alkyl, dibenzoyl, benzoyl, methylbutanoyl, methylpropanoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, alkanoyl substituted phenyl, alkenoyl substituted phenyl, aryl, acyl, heterocylic, heteroraryl, alkenylcarbonyl, ethanoyl, propanoyl, propenoyl, butanoyl, butenoyl, pentanoyl, hexenoyl, heptanoyl, heptenoyl, octanoyl, octenoyl, nonanoyl, nonenoyl, decanoyl, decenoyl, propionyl, 2-propenoyl, 2-butenoyl, Isobutyryl, 2- methylpropanoyl, 2-ethylbutyryl, ethylbutanoyl, 2-ethylbutanoyl, butyryl, (E)-2,3- Dimethylacryloyl, (E)-2-Methylcrotonoyl, 3-c/s-Methyl-methacryloyl, 3-Methyl-2-butenoyl, 3-Methylcrotonoyl, 4-Pentenoyl, (2E)-2-pentenoyl, Caproyl, 5-Hexenoyl, Capryloyl, Lauroyl, Dodecanoyl, Myristoyl, Tetradecanoyl, Oleoyl, C(2-18) Acyl, at a pentacyclic triterpene, triterpene, triterpeniod, triterpeniod saponin, terpene, isoprene or compound selected from formulae of the present application, produces inhbition of cancer growth, cancer invasion, cells invasion, cancer cell invasion, cell adhesion, cell circulation or cell attachment . This invention shows that the presence of group selected from acetyl, angeloyl, tigloyl, senecioyl, Crotonoyl, 3,3-Dimethylartyloyl, Cinnamoyl, Pentenoyl, Hexanoyl, benzoyl, Ethylbutyryl, alkyl, dibenzoyl, benzoyl, methylbutanoyl, methylpropanoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, alkanoyl substituted phenyl, alkenoyl substituted phenyl, aryl, acyl, heterocylic, heteroraryl, alkenylcarbonyl, ethanoyl, propanoyl, propenoyl, butanoyl, butenoyl, pentanoyl, hexenoyl, heptanoyl, heptenoyl, octanoyl, octenoyl, nonanoyl, nonenoyl, decanoyl, decenoyl, propionyl, 2-propenoyl, 2- butenoyl, Isobutyryl, 2-methylpropanoyl, 2-ethylbutyryl, ethylbutanoyl, 2-ethylbutanoyl, butyryl, (E)-2,3-Dimethylacryloyl, (E)-2-Methylcrotonoyl, 3-c/s-Methyl-methacryloyl, 3- Methyl-2-butenoyl, 3-Methylcrotonoyl, 4-Pentenoyl, (2E)-2-pentenoyl, Caproyl, 5- Hexenoyl, Capryloyl, Lauroyl, Dodecanoyl, Myristoyl, Tetradecanoyl, Oleoyl, C(2-18) Acyl at carbon position 21 , 22, 24 and/or 28 of a pentacyclic triterpene, triterpene, triterpeniod, triterpeniod saponin or compound selected from formulae of the present application, produces inhibition of cancer growth, cancer invasion, cells invasion, cancer cell invasion or macromolecular cell invasion. In an embodiment, the presence of group(s) selected from acetyl, angeloyl, tigloyl, senecioyl, Crotonoyl, 3,3- Dimethylartyloyl, Cinnamoyl; Pentenoyl, Hexanoyl, benzoyl, Ethylbutyryl, alkyl, dibenzoyl, benzoyl, methylbutanoyl, methylpropanoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, alkanoyl substituted phenyl, alkenoyl substituted phenyl, aryl, acyl, heterocylic, heteroraryl, alkenylcarbonyl, ethanoyl, propanoyl, propenoyl, butanoyl, butenoyl, pentanoyl, hexenoyl, heptanoyl, heptenoyl, octanoyl, octenoyl, nonanoyl, nonenoyl, decanoyl, decenoyl, propionyl, 2-propenoyl, 2-butenoyl, Isobutyryl, 2- methylpropanoyl, 2-ethylbutyryl, ethylbutanoyl, 2-ethylbutanoyl, butyryl, (E)-2,3- Dimethylacryloyl, (E)-2-Methylcrotonoyl, 3-c/s-Methyl-methacryloyl, 3-Methyl-2-butenoyl, 3-Methylcrotonoyl, 4-Pentenoyl, (2E)-2-pentenoyl, Caproyl, 5-Hexenoyl, Capryloyl, Lauroyl, Dodecanoyl, Myristoyl, Tetradecanoyl, Oleoyl, C(2-18) Acyl at carbon position 3, 8, 15, 21 , 22, 23, 24 and/or 28 of a triterpene, triterpeniod, triterpeniod saponin or compound selected from formulae of the present application produces activities including inhibition of cancer growth, cancer invasion, cells invasion, cancer cell invasion, cell adhesion, cell attachment or cell circulating wherein the group may attached with an O, S, NH, CH20 to the carbon of triterpene, triterpeniod, triterpeniod saponin or compound selected from formulae of the present application; wherein the group may be selected from group of CH20-angeloyl, CH20-tigloyl, CH20-senecioyl, CH20-acetyl, CH20-Crotonoyl, CH20-3,3-Dimethylartyloyl, CH20-Cinnamoyl, CH20- Pentenoyl, CH20-Hexanoyl, CH20-benzoyl, CH20-Ethylbutyryl, CH3, CH20H, CH20- alkyl, CH20-dibenzoyl, CH20-benzoyl, CH20-alkanoyl, CH20-alkenoyl, CH20-benzoyl alkyl substituted O-alkanoyl, CH20-alkanoyl substituted phenyl, CH20-alkenoyl substituted phenyl, CH20-aryl, CH20-acyl, CH20-heterocylic, CH20-heteroraryl, CH20-alkenylcarbonyl, CH20-ethanoyl, CH20-propanoyl, CH20-propenoyl, CH20- butanoyl, CH20-butenoyl, CH20-pentanoyl, CH20-hexenoyl, CH20-heptanoyl, CH20- heptenoyl, CH20-octanoyl, CH20-octenoyl, CH20-nonanoyl, CH20-nonenoyl, CH20- decanoyl, CH20-decenoyl, CH20-propionyl, CH20-2-propenoyl, CH20-2-butenoyl, CH20-lsobutyryl, CH20-2-methylpropanoyl, CH20-2-ethylbutyryl, CH20-ethylbutanoyl, CH20-2-ethylbutanoyl, CH20-butyryl, CH20-(E)-2,3-Dimethylacryloyl, CH20-(E)-2- ethylcrotonoyl, CH20-3-c/s-Methyl-methacryloyl, CH20-3-Methyl-2-butenoyl, CH20- 3-Methylcrotonoyl, CH20-4-Pentenoyl, CH20-(2E)-2-pentenoyl, CH20-Caproyl, CH20- 5-Hexenoyl, CH20-Capryloyl, CH20-Lauroyl, CH20-Dodecanoyl, CH20- yristoyl, CH20-Tetradecanoyl, CH20-Oleoyl, CH20-C(2-18) Acyl, (CnH2n)0-angeloyl, (CnH2n)0-tigloyl, (CnH2n)0-senecioyl, (CnH2n)0-acetyl, (CnH2n)0-Crotonoyl, (CnH2n)0-3,3-Dimethylartyloyl, (CnH2n)0-Cinnamoyl, (CnH2n)0-Pentenoyl, (CnH2n)0-Hexanoyl, (CnH2n)0-benzoyl, (CnH2n)0-Ethylbutyryl, (CnH2n)0-alkyl, (CnH2n)0-dibenzoyl, (CnH2n)0-benzoyl, (CnH2n)0-alkanoyl, (CnH2n)0-alkenoyl, (CnH2n)0-benzoyl alkyl substituted O-alkanoyl, (CnH2n)0-alkanoyl substituted phenyl, (CnH2n)0-alkenoyl substituted phenyl, (CnH2n)0-aryl, (CnH2n)0 acyl, (CnH2n)0- heterocylic, (CnH2n)0-heteroraryl, (CnH2n)0-alkenylcarbonyl, (CnH2n)0-alkane, (CnH2n)0-alkene and (CnH2n)0-sugar moiety, wherein n is 1 or 2 or 3 or 4 or over 5. In an embodiment, the presence of group at carbon position 24, produces activities. In an embodiment, the presence of group at carbon position 24 and 28 produces activities. In an embodiment, the presence of group at carbon position 24 and 21 produces activities. In an embodiment, the presence of group at carbon position 24, 28 and 21 , produces activities. In an embodiment, the presence of group at carbon position 24, 28 and 22 produces activities. In an embodiment, the presence of group at carbon position 24, 28 and 3 produces activities. In an embodiment, the presence of group at carbon position 24, and 3 produces activities. In an embodiment, the presence of group at carbon position 28 and 3 produces activities. In an embodiment, the presence of group at carbon position 3 produces activities. In an embodiment, the presence of group at carbon position 21 and 22 produces activities. In an embodiment, the hemolytic activity of the compound is reduced.
This invention shows a method of synthesizing active compound by attaching functional group to a core compound, wherein the functional group(s) comprises a group which is/are selected from ethanoyl, propanoyl, propenoyl, butanoyl, butenoyl, pentanoyl, pentenoyl, hexanoyl, hexenoyl, heptanoyl, heptenoyl, octanoyl, octenoyl, nonanoyl, nonenoyl, decanoyl, decenoyl, propionyl, 2-propenoyl, crotonoyl, 2-butenoyl, Isobutyryl, methylpropanoyl ,2-methylpropanoyl, ethylbutyryl, 2-ethylbutyryl, ethylbutanoyl, 2- ethyibutanoyl, butyryl, (E)-2,3-Dimethylacryloyl, (E)-2-Methylcrotonoyl, 3-c/s-Methyl- methacryloyl, 3-Methyl-2-butenoyl, 3-Methylcrotonoyl, 4-Pentenoyl, (2E)-2-pentenoyl, Caproyl, 5-Hexenoyl, Capryloyl, Lauroyl, Dodecanoyl, Myristoyl, Tetradecanoyl, Oleoyl, tigloyl, angeloyl, acetyl, crotonoyl, 3,3-Dimethylartyloyl, senecioyl, cinnamoyl, benzoyl, ethylbutyryl, dibenzoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, alkanoyl substituted phenyl, alkenoyl substituted phenyl, aryl, acyl, heterocylic, and heteroraryl, wherein the core compound is a 5 ring triterpene. In embodiment, the core compound is a 4 ring terpene. In embodiment, the core compound is a 3 ring terpene. In embodiment, the core compound is a 2 ring terpene. In embodiment, the core compound is a 1 ring terpene. The compounds provided in the invention are for treating cancers, inhibition of cancer growth, cancer invasion, cells invasion, cancer cell invasion; cell adhesion, cell attachment, cell circulating; for treating mad cow disease; treating prion diseases; for inhibiting viruses; for preventing cerebral aging; for improving memory; improving cerebral functions; for curing enuresis, frequent micturition, urinary incontinence; dementia, Alzheimer's disease, autism, brain trauma, Parkinson's disease or other diseases caused by cerebral dysfunctions or neurodegeneration; for treating arthritis, rheumatism, poor circulation, arteriosclerosis, Raynaud's syndrome, angina pectoris, cardiac disorder, coronary heart disease, headache, dizziness, kidney disorder; cerebrovascular diseasea; inhibiting NF-kappa B activation; for treating brain edema, severe acute respiratory syndrome, respiratory viral diseases, chronic venous insufficiency, hypertension, chronic venous disease, oedema, inflammation, hemorrhoids, peripheral edema formation, varicose vein disease, flu, post traumatic edema and postoperative swelling; for inhibiting blood clots, for inhibiting ethanol absorption; for lowering blood sugar; for regulating adrenocorticotropin and corticosterone levels. This invention provides a composition for Anti-MS, anti-aneurysm, anti-asthmatic, anti-oedematous, anti-inflammatory, anti-bradykinic, anti- capillarihemorrhagic, anti-cephalagic, anti-cervicobrachialgic, anti-eclamptic, anti- edemic, anti-encaphalitic, anti-epiglottitic, anti-exudative, anti-flu, anti-fracture, anti- gingivitic, anti-hematomic, anti-herpetic, anti-histaminic, anti-hydrathritic, anti-meningitic, antioxidant, anti-periodontic, anti-phlebitic, anti-pleuritic, anti-raucedo, anti-rhinitic, anti- tonsilitic, anti-ulcer, anti-varicose, anti-vertiginous, cancerostatic, corticosterogenic, diuretic, fungicide, hemolytic, hyaluronidase inhibitor, lymphagogue, natriuretic, pesticide, pituitary stimulant, thymolytic, vasoprotective, inhibiting leishmaniases, modulating adhesion or angiogenesis of cells, anti-parasitic; increase the expression of the genes: ANGPT2, DDIT3, LIF and NFKB1 Z, and manufacturing an adjuvant composition and venotonic treatment.
Experiments presented in this invention showed that the compound AKOH has no effect in inhibiting cancer growth, cancer invasion, cells invasion or cancer cell invasion. AKOH was obtained by removing the angeloyi groups from carbon positions 21 and 22 of the active Xanifolia Y(Y3). This invention shows that the ability for inhibiting cancer invasion, cells invasion or cancer cell invasion of Xanifolia Y(Y3) are lost by removing angeloyi groups from carbon positions 21 and 22.
Experiments presented in this invention showed that the core compound including E4A, E5A, Xanifolia Y-core have no effect in inhibiting cancer growth, cancer invasion, cells invasion or cancer cell invasion. Xanifolia Y-core was obtained by removing the angeloyi groups from carbon positions 21 and 22, and the sugar moieties from carbon 3 of the active Xanifolia Y(Y3). E4A (E IV A) was obtained by removing the groups from carbon positions 3, 21 and 22 of the active Escin. E5A (E V A) was obtained by removing the groups from carbon positions 3, 21 and 22 of the active Escin. This invention showed that the core compound including E4A, E5A, Xanifolia Y-core and AKOH have no hemolytic activity and no anti-cancer activity.
This invention showed that functional group attached at carbon position 24 of a triterpene did not produce hemolytic activity, which has bio-activities including inhibiting cancer growth, inhibiting cancer invasion, cells invasion or cancer cell invasion. This invention showed that function group(s) attached at carbon position 24 and 1 or 2 or 3 of carbon position 28, 21 , 22 of a triterpene did not produce hemolytic activity, which has bio-activities including inhibiting cancer growth, inhibiting cancer invasion, cells invasion or cancer cell invasion.
This invention provides a triterpene with reduced hemolytic activity for treating diseases, wherein the triterpene comprising a group(s) attached at its core producing bio- activities. This invention provides a triterpene with reduced hemolytic activity comprising a group(s) attached at carbon position 24, or carbon position 24 and 1 or 2 or 3 of of other position(s) of a triterpene, which has bio-activities. This invention provides a composition comprising a triterpene with reduced hemolytic activity comprising a group(s) attached at carbon position 24, or carbon position 24 and 1 or 2 or 3 of of other position(s) of a triterpene, which has bio-activities. This invention provides a method for bio-ativities treatment including but not limited to treating cancers, comprising administering to said subject an effective amount of compound, wherein the compound is a triterpene with reduced hemolytic activity comprising a group(s) attached at carbon position 24, or carbon position 24 and 1 or 2 or 3 of of other position(s) of a triterpene, which has bio-activities.
This invention showed that Tig-N, Tig -Q, Tig -R, Tig-T Tig-S and Tig-V do not have hemolytic activity up to 20 ug/ml. The original compound ES lyse 100% red blood cells (RBC) at 5 ug/ml. Compare to Y3, the ACH-Y3 is less potent in hemolytic activity. Tig-R has no hemolytic activity. This invention showed that Tig-N, Tig -Q, Tig -R, Tig-T Tig-S and Tig-V have anti cancer activities.
Many saponins and triterpenes have hemolytic characteristic that damage red blood cells. This severe side effect make people hesitate to use saponins or triterpenes in medicines. This invention produces sythesised saponins and triterpenes with reduced hemolytic characteristic for use as medicament. This invention produces compounds with reduced hemolytic characteristic for use as medicament. The medicament can be used for treating cancer, inhibiting cancer growth, cancer invasion, cells invasion or cancer cell invasion.
This invention shows that the ability for inhibiting cancer growth, cancer invasion, cells invasion or cancer cell invasion are maintained when the sugar moieties are removed from carbon position 3 of an active compound, triterpene, triterpeniod, or triterpeniod saponin. Experiments presented in this invention showed that the compound ACH-Y3 has the ability to inhibit cancer invasion, cells invasion or cancer cell invasion. The compound ACH-Y3 was obtained by removing the sugar moieties from carbon position 3 of a active Xanifolia Y(Y3). This invention shows that the ability for inhibiting cancer invasion, cells invasion or cancer cell invasion are maintained when the sugar moieties are removed from the carbon position 3 of active Xanifolia Y(Y3).
A compound which has bio-activities including inhibiting cancer growth, inhibiting cancer invasion, cells invasion or cancer cell invasion is called active compound.
This invention provides a use for compounds, compositions, and methods for manufacturing medicament for for treating cancers, inhibition of cancer growth, cancer invasion, cells invasion, cancer cell invasion; cell adhesion, cell attachment, cell circulating, or for inhibiting cancer metastasis, wherein the compounds comprise the structures selected from the formulae of the present application, wherein the compounds can be synthesized or isolated, wherein the compounds comprise the pentacyclic triterpenes, wherein the compounds with reduced hemolytic, wherein the cells comprise cancer cells, wherein the cancers comprise breast cancer, leukocytic cancer, liver cancer, ovarian cancer, bladder cancer, prostatic cancer, skin cancer, bone cancer, brain cancer, leukemia cancer, lung cancer, colon cancer, CNS cancer, melanoma cancer, renal cancer, cervical cancer, esophageal cancer, testicular cancer, spleenic cancer, kidney cancer, lymphhatic cancer, pancreatic cancer, stomach cancer and thyroid cancer.. The method of inhibiting cancer invasion, cells invasion or cancer cell invasion activities uses non-cytotoxic drug concentrations. The method of inhibiting metastasis uses non-cytotoxic drug concentrations. There is no noticeable change in cell morphology.
This invention provides triterpene(s) with reduced hemolytic activity for treating diseases, wherein the triterpene comprising a group(s) attached at its core producing bio-activities. This invention provides a triterpene with reduced hemolytic effect, comprising a group(s) attached at carbon position 24, or carbon position 24 and 1 or 2 or 3 of of other position(s) of a triterpene, which has bio-activities. This invention provides a composition comprising a triterpene with reduced hemolytic activity comprising a group(s) attached at carbon position 24, or carbon position 24 and 1 or 2 or 3 of of other position(s) of a triterpene, which has bio-activities. This invention provides a method for bio-ativities treatment including but not limited to treating cancers, comprising administering to said subject an effective amount of compound, wherein the compound is a triterpene with reduced hemolytic activity, comprising a group(s) attached at carbon position 24, or carbon position 24 and 1 or 2 or 3 of of other position(s) of a triterpene, which has bio-activities, wherein a compound selected from A1 -18, A20-32, B1 -18, B20-32, C1 -18, C20-32, D1 -18, D20-32, D1 -18, D20-32, D1 -18, D20-32, D1 -18, D20-32, D1 -18, D20-32, E1 -18, E20-32, G1 -18, G20-32, H1 -18, H20-32, 11 -18, 120-32, J1 -18, J20-32, K1-18, K20-32, Tig-Sen-n, Tig-Cro-n, Tig-Acy-n, Tig-Pen- n, Tig-Hex-n, Tig-Cin-n, Tig-Ang-n, Tig-Eth-n, Tig-R-Sen-n, Tig-R-Cro-n, Tig-R-Acy-n, Tig-R-Pen-n, Tig-R-Hex-n, Tig-R-Cin-n, Tig-R-Ang-n, Tig-R-Eth-n, wherein n=1 to 6, and a salt, ester, metabolite thereof, and the compounds selected from formulae 2A, and K; wherein the compound is selected fromTig-N, Tig -Q, Tig -R, Tig-T Tig-S and Tig-V. This invention provides methods for treating cancers, inhibition of cancer growth, cancer invasion, cells invasion, cancer cell invasion; cell adhesion, cell attachment, cell circulating, migration, metastasis or growth of cancers, wherein the methods comprise affecting gene expression, wherein the methods comprise stimulating gene expression, or wherein the methods comprise inhibiting the gene expression, or wherein the methods comprise administering to a subject an effective amount of compounds, compositions in this application. In an embodiment, the method comprises contacting said cell with a compound selected from A1 -18, A20-32, B1 -18, B20-32, C1 -18, C20-32, D1 -18, D20-32, D1 -18, D20-32, D1 -18, D20-32, D1 -18, D20-32, D1 -18, D20-32, E1 -18, E20-32, G1 -18, G20-32, H1 -18, H20-32, 11 -18, 120-32, J1 -18, J20-32, K1 -18, K20-32, Xanifolia Y0, Y1 , Y2, Y(Y3), Y5, Y7, Y8, Y9, Y10, Xanifolia (x), M10, Escin(bES), Aescin, ACH-Y(Y3), ACH-Y10, ACH-Y2, ACH-Y8, ACH-Y7, ACH-YO, ACH-X, ACH-Z4, ACH-Z1 , ACH-Escin(bES), ACH-M10, Tig-Sen-n, Tig-Cro-n, Tig-Acy-n, Tig-Pen-n, Tig-Hex-n, Tig-Cin-n, Tig-Ang-n, Tig-Eth-n, Tig-R-Sen-n, Tig-R-Cro-n, Tig-R-Acy-n, Tig-R-Pen-n, Tig-R-Hex-n, Tig-R-Cin-n, Tig-R-Ang-n, Tig-R-Eth-n, wherein n=1 to 6, and a salt, ester, metabolite thereof, and the compounds selected from formulae 2A, and K. In vitro studies show that a compound selected from structure (2A) or (K) inhibits cell adhesion to culture flasks. The compound blocks the function of these adhesive molecules on cells. In an embodiment, the selected compound blocks the function of these adhesive molecules on cells. In an embodiment, the selected compound blocks the function of these adhesive molecules on carcinoma cells. In an embodiment, the selected compound blocks the function of these adhesive molecules on the mesothelial cells. This invention provides an anti adhesion therapy which uses the compound as a mediator or inhibitor of adhesion proteins and angiopoietins. It inhibits excess adhesion and inhibits cell attachment. This invention provides compounds for use as a mediator for cell circulating, cell moving and inflammatory diseases. In an embodiment, the selected compound binds to the adhesive proteins (by masking) on the membrane and inhibits the interaction of adhesion proteins with their receptors. In an embodiment, the selected compound's action on the membrane affects adhesion proteins' function in the membrane. The lost of adhesion activity of cancer cells is result from direct or indirect action of the selected compound on membrane proteins. (Our purification methods and biological assays include the MTT assay in International Application No. PCT/US05/31900, filed September 7, 2005, U.S. Serial No. 1 1/289,142, filed November 28, 2005, and U.S. Serial No. 11/131551 , filed May 17, 2005, and PCT/US2008/002086, 1 188-ALA-PCT, filed February 15, 2008, the cell invasion experiments methods in International Application PCT/US2010/0042240, filed July 16, 2010)
This invention provides a use of compounds or methods for inhibiting cancer invasion, cell invasion, cancer cell invasion, macromolecular cell invasion, migration, metastasis or growth of cancers, wherein this invention comprises a process and method for administration of the composition, wherein administration is by intravenous injection, intravenous drip, intraperitoneal injection or oral administration; wherein administration is by intravenous drip: 0.003-0.03 mg/kg body weight of compound dissolved in 250 ml of 10% glucose solution or in 250 ml of 0.9% NaCI solution, or by intravenous injection: 0.003-0.03 mg/kg body weight per day of compound dissolved in 10-20 ml of 10% glucose solution or of 0.9% NaCI solution, or 0.01 -0.03 mg/kg body weight of compound dissolved in 250 ml of 10% glucose solution or in 250 ml of 0.9% NaCI solution, or by intravenous injection: 0.01 -0.03 mg/kg body weight per day of compound dissolved in 10-20 ml of 10% glucose solution or of 0.9% NaCI solution, or 0.01 -0.05 mg/kg body weight of compound dissolved in 250 ml of 10% glucose solution or in 250 ml of 0.9% NaCI solution, or by intravenous injection: 0.01 -0.05 mg/kg body weight per day of compound dissolved in 10-20 ml of 10% glucose solution or of 0.9% NaCI solution, or 0.05-0.2 mg/kg body weight of compound dissolved in 250ml of 10% glucose solution or in 250 ml of 0.9% NaCI solution, or by intravenous injection: 0.05-0.2 mg/kg body weight per day of compound dissolved in 10-20 ml of 10% glucose solution or of 0.9% NaCI solution, or by intravenous drip: 0.1 -0.2 mg/kg body weight per day of compound dissolved in 250ml of 10% glucose solution or in 250ml of 0.9% NaCI solution, or by intravenous injection: 0.1 -0.2 mg/kg body weight per day compound dissolved in 10-20 ml of 10% glucose solution or of 0.9% NaCI solution, or by intraperitoneal injection(I.P.): 2.5 mg/kg body weight per day compound dissolved in 10% glucose solution or of 0.9% NaCI solution, or by oral administration wherein the dosage of mammal is 1 -10 mg/kg, 10-30 mg/kg, 30-60 mg/kg, or 60-90 mg/kg body weight of compound, or by intravenous injection or intravenous drip wherein the dosage of mammal is 0.01 -0.1 mg/kg body weight , 0.1 -0.2 mg/kg, 0.2 - 0.4 mg/kg body weight, or 0.4-0.6 mg/kg body weight of compound, or by intraperitoneal injection (I .) wherein the dosage of mammal is 1 -3 mg/kg, 3-5 mg/kg, 4-6 mg/kg, or 6-10 mg/kg body weight of compound.
This invention provides a use of compounds or methods for treating cancers, inhibition of cancer growth, cancer invasion, cells invasion, cancer cell invasion; macromolecular cell invasion, cell adhesion, cell attachment, cell circulating, migration, metastasis or growth of cancers, infection or re-infection of virus or infectious macromolecules, and cancer cell fusion, wherein the invention comprises a pharmaceutical composition comprising the compound of this invention or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent, wherein said compound is present in a concentration of 0.01 ug/ml to 65 ug/ml, or wherein said compound is present in a concentrat ion of 0.01 ug/ml to 40 ug/ml, or wherein said compound is present in a concentrat ion of 0.01 ug/ml to 30 ug/ml, or wherein said compound is present in a concentrat ion of 0.01 ug/ml to 10 ug/ml, or wherein said compound is present in a concentrat ion of 0.01 ug/ml to 5ug/ml, or wherein said compound is present in a concentrat ion of 5ug/ml to 10ug/ml, or wherein said compound is present in a concentrat ion of 0.1 ug/ml to 5ug/ml, or wherein said compound is present in a concentrat ion of 0.1 ug/ml to 7.5ug/ml, or wherein said compound is present in a concentrat ion of 0.1 ug/ml to 10ug/ml, or wherein said compound is present in a concentrat ion of 0.1 ug/ml to 15ug/ml, or wherein said compound is present in a concentrat ion of 0.1 ug/ml to 20ug/ml, or wherein said compound is present in a concentrat ion of 0.1 ug/ml to 30ug/ml, or wherein said compound is present in a concentrat ion of 1 ug/m to 5ug/ml, or wherein said compound is present in a concentrat ion of 1 ug/ml to 7.5ug/ml, or wherein said compound is present in a concentrat ion of 1 ug/ml to 10ug/ml, or wherein said compound is present in a concentrat ion of 1 ug/ml to 15ug/ml, or wherein said compound is present in a concentrat ion of 1 ug/ml to 20ug/ml, or wherein said compound is present in a concentrat ion of 1 ug/ml to 30ug/ml, or wherein said compound is present in a concentrat ion of 3ug/ml to 5ug/ml, or wherein said compound is present in a concentrat ion of 3ug/ml to 7.5ug/ml, or wherein said compound is present in a concentrat ion of 3ug/ml to 10ug/ml, or wherein said compound is present in a concentrat ion of 3ug/ml to 15ug/ml, or wherein said compound is present in a concentrat ion of 3ug/ml to 20ug/ml, or wherein said compound is present in a concentrat ion of .3ug/ml to 30ug/ml, or wherein said compound is present in a concentrat ion of 4ug/ml to 5ug/ml, or wherein said compound is present in a concentrat ion of 4ug/ml to 7.5ug/ml, or wherein said compound is present in a concentrat ion of 4ug/ml to 10ug/ml, or wherein said compound is present in a concentrat ion of 4ug/ml to 15ug/ml, or wherein said compound is present in a concentrat ion of 4ug/ml to 20ug/ml, or wherein said compound is present in a concentrat ion of 4ug/ml to 30ug/ml, or wherein said compound is present in a concentrat ion of 5ug/ml to 8ug/ml, or wherein said compound is present in a concentrat ion of 5ug/ml to 9ug/ml, or wherein said compound is present in a concentration of 5ug/ml to l Oug/ml, or wherein said compound s present in a concentration of 5ug/ml to 15ug/ml, or wherein said compound s present in a concentration of 5ug/ml to 20ug/ml, or wherein said compound s present in a concentration of 5ug/ml to 30ug/ml, or wherein said compound s present in a concentration of 7ug/ml to 8ug/ml, or wherein said compound s present in a concentration of 7ug/ml to 9ug/ml, or wherein said compound s present in a concentration of 7ug/ml to l Oug/ml, or wherein said compound s present in a concentration of 7ug/ml to 15ug/ml, or wherein said compound s present in a concentration of 7ug/ml to 20ug/ml, or wherein said compound s present in a concentration of 7ug/ml to 30ug/ml.
This invention provides a use of compounds or methods for treating cancers, inhibition of cancer growth, cancer invasion, cells invasion, cancer cell invasion; macromolecular cell invasion, cell adhesion, cell attachment, cell circulating, migration, metastasis or growth of cancers, infection or re-infection of virus or infectious macromolecules, and cancer cell fusion, wherein the invention comprises a pharmaceutical composition comprising the compound of this invention or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent, wherein said compound is present in a concentration of 0.008u to 80uM, or wherein said compound is present in a concentration of 0.01 uM to 60uM, or wherein said compound is present in a concentration of 0.01 uM to 50uM, or wherein said compound is present in a concentration of 0.01 uM to 40uM, or wherein said compound is present in a concentration of 0.01 uM to 30uM, or wherein said compound is present in a concentration of 0.01 uM to 20uM, or wherein said compound is present in a concentration of 0.01 uM to 10uM, or wherein said compound is present in a concentration of 5uM to 10uM, or wherein said compound is present in a concentration of 0.1 uM to 5u , or wherein said compound is present in a concentration of 0.1 uM to 7.5uM, or wherein said compound is present in a concentration of 0.1 uM to 10uM, or wherein said compound is present in a concentration of 0.1 uM to 15u , or wherein said compound is present in a concentration of 0.1 uM to 20uM, or wherein said compound is present in a concentration of 0.1 uM to 30uM or wherein said compound is present in a concentration of 0.1 uM to 40uM, or wherein said compound is present in a concentration of 0.1 uM to 50uM or wherein said compound is present in a concentration of 0.1 uM to 60uM, or wherein said compound is present in a concentration of 0.1 uM to 80uM, or wherein said compound is present in a concentration of 1 uM to 5uM, or wherein said compound is present in a concentration of 1 uM to 7.5u , or wherein said compound is present in a concentration of 1uM to 10uM, or wherein said compound is present in a concentration of 1 uM to 15uM, or wherein said compound is present in a concentration of 1 uM to 20uM, or wherein said compound is present in a concentration of 1 uM to 30uM or wherein said compound is present in a concentration^ 1 uM to 40uM, or wherein said compound is present in a concentration of 1 uM to 50uM or wherein said compound is present in a concentration of 1 uM to 60uM, or wherein said compound is present in a concentration of 1 uM to 80uM, or wherein said compound is present in a concentration of 3uM to 5uM, or wherein said compound is present in a concentration of 3uM to 7.5u , or wherein said compound is present in a concentration of 3uM to 10uM, or wherein said compound is present in a concentration of 3uM to 15uM, or wherein said compound is present in a concentration of 3uM to 20uM, or wherein said compound is present in a concentration of 3uM to 30uM or wherein said compound is present in a concentration of 3uM to 40uM, or wherein said compound is present in a concentration of 3 uM to 50uM or wherein said compound is present in a concentration of 3 uM to 60uM, or wherein said compound is present in a concentration of 3uM to 80uM, or wherein said compound is present in a concentration of 5uM to 8uM, or wherein said compound is present in a concentration of 5uM to 10uM, or wherein said compound is present in a concentration of 5uM to 15u , or wherein said compound is present in a concentration of 5uM to 20uM, or wherein said compound is present in a concentration of 5uM to 30uM or wherein said compound is present in a concentration of 5uM to 40uM, or wherein said compound is present in a concentration of 5uM to 50uM or wherein said compound is present in a concentration of 5uM to 60uM, or wherein said compound is present in a concentration of 5uM to 80uM. or wherein said compound is present in a concentration of 7uM to 8uM, or wherein said compound is present in a concentration of 7uM to 10uM, or wherein said compound is present in a concentration of 7uM to 15uM, or wherein said compound is present in a concentration of 7uM to 20uM, or wherein said compound is present in a concentration of 7uM to 30uM or wherein said compound is present in a concentration of 7uM to 40uM, or wherein said compound is present in a concentration of 7uM to 50uM or wherein said compound is present in a concentration of 7uM to 60uM, or wherein said compound is present in a concentration of 7uM to 80uM.
The invention will be better understood by reference to the Experimental Details which follow, but those skilled in the art will readily appreciate that the specific experiments detailed are only illustrative, and are not meant to limit the invention as described herein, which is defined by the claims which follow thereafter. Throughout this application, various references or publications are cited. Disclosures of these references or publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art to which this invention pertains.
It is to be noted that the transitional term "comprising", which is synonymous with "including", "containing" or "characterized by", is inclusive or open-ended and does not exclude additional, un-recited elements or method steps. Example 1
Tablet for dose containing 10mq. 20mq 30mq of active compound
Active compound 1 mg 5mg 10mg 20mg 30mg
Microcrystalline cellulose 20mg 20mg 19.75mg 60mg 100mg Corn starch 29mg 24.5mg 19.75mg 19.25mg 18.5mg
Magnesium stearate Omg 0.5mg 0.5mg 0.75mg 1.5mg
The active compound, cellulose, and a portion of the corn starch are mixed and granulated to 10% corn starch paste. The resulting granulation is sieved, dried and blended with the remainder of the corn starch and the magnesium stearate. The resulting granulation is then compressed into tablets containing 1 , 5, 10, 20, 30mg, respectively of active ingredient per tablet.
Example 2
Intravenous solution preparation
An intravenous dosage form of the active compound is prepared as follows:
Active compound 1 -1 Oug
Sodium citrate 5-50 mg
Citric acid 1 -15 mg
Sodium chloride 1 -8 mg
Water for injection (USP) q.s. to 1 ml_
Utilizing the above quantities, the active compound is dissolved at room temperature in a prepared solution of sodium chloride, citric acid, and sodium citrate in water for injection.
Example 3
Intravenous drip preparation
0.25-2.5mg compound dissolved in 250ml of 10% glucose solution or in 250ml of 0.9% NaCI solution. Intravenous drip preparation: 1 -2.mg compound dissolved in 250ml of 10% glucose solution or in 250ml of 0.9% NaCI solution
Treatment of angelic acid with one of the many standard chlorinating reagents including phosphorus ocychloride, phosphorus trichloride and thionyl chloride produces tigloyi chloride. Oxalyl chloride produces a 2:1 ratio of angeloyl chloride to tigloyi chloride. Treatment of potassium salt in diethyl ether with oxalyl chloride and catalytic DMF for 2 hr at 0C produces pure angeloyl chloride.
Acid Hydrolysis of the following compounds:
a) Xanifolia(Y),
chemical name
galactopyranosyl (1→2)]-oc-L-arabinofuranosy (1→3)- -D-glucuronopyranosyl-21 ,22-0- diangeloyl-3 , 15a, 16a, 21 β, 22a, 28-hexahydroxyolean-12-ene;
c) Xanifolia (Y2),
or chemical name: 3-0-[β-ϋ- glucopyranosyl-(1 ->2)]-a-L-arabinofuranosy (1→3)- -D-glucuronopyranosyl-21 ,22-0- diangeloyl-3p, 15a, 16a, 21 β, 22a, 24β, 28-heptahydroxyolean-12-ene; d) Xanifolia (Y8),
or chemical name: 3-0-[ ?-glucopyranosyl (1→2)]-«-arabinofuranosyl (1→3)- ?-glucuronopyranosyl-21 , 22-Odiangeloyl-3 7, 16a, 21/?, 22or, 24β, 28-hexahydroxyolean-12-ene; f) Xanifolia (Y10),
or chemical name:
3-0-[ kjalactopyranosyl (1→2)]-a-arabinofuranosyl (1→3)- ?-glucuronopyranosyl-21 , 22-0-diangeloyl-3/?, 16or, 21 β, 22a, 28-pentahydroxyolean-12-ene. j) structure (M 10)
m structure (bES):
The composition comprises bioactive compounds from natural plants or synthesis. The program is based on our purification methods and biological assays including the MTT assay. See International Application No. PCT/US05/31900, filed September 7, 2005, U.S. Serial No. 1 1/289,142, filed November 28, 2005, and U.S. Serial No. 1 1/131551 , filed May 17, 2005, and PCT/US2008/002086, 1 188-ALA-PCT, filed February 15, 2008, 12/344,682, 1020-B1 -US, filed December 29, 2008. The details of Analysis of gene expression of ES2 cells after Y-treatment by Microarray, Data Analysis Methods and Western blot in PCT/US2008/002086, 1 188-ALA-PCT, filed February 15, 2008, and the cell invasion experiments methods in International Application PCT/US2010/0042240, filed July 16, 2010.
The Haemolytic Assay
Erythrocytes (RBC) were isolated from human blood (EDTA whole blood, collected randomly). 50ul of the 10% RBC suspension (in PBS) was added to 2 ml of sample solutions (concentration range from 0.1 ug/ml to 400 ug/ml) in PBS. The mixture was vortexed briefly and sat for 60 min at room temperature. The mixture was spun at 3K for 10 min and the relative amounts of lysed. hemoglobin in the supernatant were measured at 540 nm. The synthetic compounds of present application were tested with this method. Acid Hydrolysis of Saponin
15mg Xanifolia-Y was dissolved in 1 ml of methanol. 1 ml of 2N HCI was then added. The mixture was refluxed in 80C water bath for 5 hours. The solution was then neutralized by adding 2ml of 1 N NaOH (to final pH 4-6). The aglycone was then extracted with ethylacetate 3ml x 2. The extracts were collected and pooled. Further isolation of aglycone (ACH-Y) was achieved by HPLC with isocratic elution of 80 -100% acetonitrile. Repeating the experiment with compounds Z4, Y10, Y2, Y8, Y7, Y0, X, M10 and ESCIN (bES) gives the following compounds respectively: ACH-Z4, ACH-Y10, ACH-Y2, ACH-Y8, ACH-Y7, ACH-Y0, ACH-X, ACH-E, ACH-Z5, ACH-M10 and ACH- bES.
Removal of the acyl group by alkaline hydrolysis
20mg of Xanifolia-Y was dissolved in 0.5ml of 1 N NaOH. The solution was incubated in 80C water bath for 4 hours. It was cooled to room temperature before being neutralized with 0.5ml 1 N HCI (adjust pH to about 3). The mixture was extracted with 2ml 1 -butanol 3 times. The butanol fractions were collected and lyophilized. The hydrolyzed saponin was further purified with HPLC in a C-18 column eluted with 25% acetonitrile. 0
Compounds AKOH-Y and AKOH-M10 do not show the ability to inhibit cancer growth, cancer invasion, cells invasion or cancer cell invasion.
Core compound
A core compound or pentacyclic triterpenes, hydroxylated triterpenes is obtained by acid and alkaline hydroysis of saponin from natural sources. A pentacyclic triterpene can also be obtained by synthetic methods. A method for synthesizing the core compound is as follows:
Beta-Escin, compound Y, Y10, Y2, Y8, Y7, Y0, X, or M10 dissolved in 1 M NaOH (20 mg/ml) was incubated at 70C for 5 hours. The hydrolyzed solution was neutralized with HCI and the water was evaporated by lyophilization. The product was dissolved in 50% methanol and 1 N HCI. The mixture was incubated at 70C for 5 hours. The solution was neutralized with NaOH. The hydrolyzed product was extracted with ethylacetate, which was subsequently removed by evaporation. Further purification of the hydrolyzed product of core compounds including (E4A) were archived with FPLC chromatography in a C18 column equilibrated with 70% acetonitrile/TFA at the flow rate of 1 ml/min. The core compounds are obtained.
The core compounds do not show the ability to inhibit cancer growth, cancer invasion, or cell adhesion. The structures of core compounds:
wherein R1 , R2, R5, R8 represent OH; R3 represents OH, H or absent; R4, R10 represent CH3 or CH20H; R9, R11 , R12, R13, R14, R15 represent CH3;
wherein R1 , R2, R5, R8, R17, R18 represent OH; R3 represents OH, H or absent; R9, R1 1 , R12, R13, R14, R15 represent CH3.
2< 23 (J);
A typical numbering 1 to 30 of carbon positions of a pentacyclic triterpene.
wherein R1 , R2, R5, R8, R17, R18 represent OH;
R9, R11 , R12, R13, R14, R15 represent CH3, also named E4A or (E). This invention provides a method of synthesizing new active compounds. A method of attaching functional groups to the core compounds including but not limited to (A), (B), (C), (D1 ), (D2), (E), (F), (G), (H1 ), (H2), (J)] involves esterification of core compounds with acyl halide, wherein the halide including chloride, bromide, fluoride and iodide, wherein the acyl halide comprises acyl chloride, wherein acyl chloride including but not limited to Tigloyl chloride, angeloyl chloride, Acetyl chloride, Crotonoyl chloride, 3,3- Dimethylartyloyl chloride, senecioyl chloride, Cinnamoyl chloride, Pentenoyl chloride, Hexanoyl chloride, benzoyl chloride, Ethylbutyryl chloride, Propionyl chloride, 2- Propenoyl chloride, Isobutyryl chloride, Butyryl chloride, (2E)-2-pentenoyl chloride, 4- Pentenoyl chloride, 5-Hexenoyl chloride, Heptanoyl chloride, Octanoyl chloride, Nonanoyl chloride, Decanoyl chloride, Lauroyl chloride, Myristoyl chloride, Oleoyl chloride for 5 sec, 1 min, 2 min, 5 min, 10 min, 30 min, 1 hr, 2 hr, 18 hr, 2 days or 3 days at OC, 25C or 75C temperature. At the end of reaction, 5 ml of 2N HCI or 1 M NaHC03 is added to the reaction mixture. The solution is then extracted 3 times with 10 ml of ethyl acetate which is then evaporated under vacuum and at 45C and lyophilization. The reaction product is dissolved in 80% acetonitrile - 0.005% Trifluoroacetic acid. The active esterification products are purified with HPLC. MTT activity was performed to test the activity of acyl chloride, solution after the reaction, individual fractions, and individual compounds. The core compounds are synthetic, semi synthetic or from natural source. The core compounds are including terpene, isoprene, triterpenes, and hydroxylated triterpenes.
MTT activity of acylation of core compounds in different reaction time period of (ASAP)5 sec, 1 min, 2 min, 5 min, 10 min, 30 min, 1 hr, 2 hr, 18 hr, 2 days or 3 days at 0C, 25C or 75C temperature were studied. HPLC profiles of esterification products of core compound E4A with acyl halide, wherein the halide comprise chloride, bromide, fluoride and iodide, wherein the acyl halide comprise acyl chloride, wherein acyl chloride comprise tigloyl chloride, angeloyl chloride, acetyl chloride, crotonoyl chloride, 3,3- dimethylartyloyl chloride, senecioyl chloride, cinnamoyl chloride, pentenoyl chloride, hexanoyl chloride, benzoyl chloride, ethylbutyryl chloride, propionyl chloride, 2- propenoyl chloride, isobutyryl chloride, butyryl chloride, (2E)-2-pentenoyl chloride, 4- Pentenoyl chloride, 5-hexenoyl chloride, heptanoyl chloride, octanoyl chloride, nonanoyl chloride, decanoyl chloride, Lauroyl chloride, myristoyl chloride, oleoyl chloride show that the compounds vary in composition when the time or temperature of the reaction is changed. See example in Figures 1 -12 and Experiments 1 -29 The peaks, fractions and compounds are selected according to the activities of times studies and the changes of peaks. Selecting the HPLC fractions for isolation is according to the cytotoxic activity of the reaction product obtained at a specific time. The compounds having strong to weak activities are selected and isolated. Selecting the HPLC fractions for isolation may be according to the cytotoxic activity of times studies and the change of peaks. The anti cancer activities are the MTT studies of bone (U20S), lung (H460), bladder(HTB-9), ovary (ES2), colon (HCT1 16), pancreas (Capan), ovary(OVCAR3), prostate (DU145), skin (SK-Mel-5), mouth (KB), kidney (A498), breast (MCF-7), liver (HepG2), brain (T98G), luekemia (K562), cervix (HeLa).
Esterification of core compound E4A with TigloyI chloride and isolation of the compounds with HPLC give the following compounds: wherein Tig=Tigloyl
R1 R2 R5 R8 R17 R18 Cytotoxicity activity
E4A OH OH OH OH OH OH none
A1 OH OH OH OH O-Tig OH moderate
A2 OH OH OH OH OH O-Tig moderate
A3 OH OH OH OH O-Tig O-Tig strong
A4 O-Tig OH OH OH O-Tig O-Tig moderate
A5 OH O-Tig OH OH O-Tig O-Tig moderate
A6 OH OH O-Tig OH O-Tig O-Tig moderate
A7 OH OH OH O-Tig O-Tig O-Tig moderate
A8 O-Tig O-Tig OH OH O-Tig O-Tig weak
A9 OH O-Tig O-Tig OH O-Tig O-Tig weak
A10 OH OH O-Tig O-Tig O-Tig O-Tig weak
A1 1 O-Tig OH O-Tig OH O-Tig O-Tig weak
A12 OH O-Tig OH O-Tig O-Tig O-Tig weak
A13 O-Tig OH OH O-Tig O-Tig O-Tig weak
A14 OH O-Tig O-Tig OH O-Tig O-Tig weak
A15 O-Tig O-Tig O-Tig OH O-Tig O-Tig weak
A16 O-Tig O-Tig OH O-Tig O-Tig O-Tig weak
A17 O-Tig OH O-Tig O-Tig O-Tig O-Tig weak
A18 OH O-Tig O-Tig O-Tig O-Tig O-Tig weak
A19 O-Tig O-Tig O-Tig O-Tig O-Tig O-Tig none
A20 O-Tig O-Tig OH OH OH O-Tig moderate
A21 O-Tig O-Tig OH OH O-Tig OH moderate
A22 O-Tig O-Tig OH O-Tig OH OH moderate
A23 O-Tig O-Tig O-Tig OH OH OH moderate
A24 O-Tig O-Tig OH OH OH OH moderate
A25 O-Tig OH OH OH OH O-Tig moderate
A26 OH O-Tig OH OH OH O-Tig moderate
A27 OH OH O-Tig OH OH O-Tig moderate
A28 OH OH OH O-Tig OH O-Tig moderate
A29 O-Tig OH OH OH O-Tig OH moderate
A30 OH O-Tig OH OH O-Tig OH moderate
A31 OH OH O-Tig OH O-Tig OH moderate A32 OH OH OH O-Tig O-Tig OH moderate
Esterification of core compound E4A with AngeloyI chloride and isolation of the compounds with HPLC give the following compounds: wherein Ang = AngeloyI
Esterification of core compound E4A with (3,3-Dimethylartyloyl chloride) senecioyl chloride and isolation of the compounds with HPLC give the following compounds:
Wherein Sen = senecioyl
R1 R2 R5 R8 R17 R18 Cytotoxicity activity
E4A OH OH OH OH OH OH none
B1 OH OH OH OH O-Sen OH moderate
B2 OH OH OH OH OH O-Sen moderate
B3 OH OH OH OH O-Sen O-Sen strong
B4 O-Sen OH OH OH O-Sen O-Sen moderate B5 OH O-Sen OH OH O-Sen O-Sen moderate
B6 OH OH O-Sen OH O-Sen O-Sen moderate
B7 OH OH OH O-Sen O-Sen O-Sen moderate
B8 O-Sen O-Sen OH OH O-Sen O-Sen weak
B9 OH O-Sen O-Sen OH O-Sen O-Sen weak
B10 OH OH O-Sen O-Sen O-Sen O-Sen weak
B1 1 O-Sen OH O-Sen OH O-Sen O-Sen weak
B12 OH O-Sen OH O-Sen O-Sen O-Sen weak
B13 O-Sen OH OH O-Sen O-Sen O-Sen weak
B14 OH O-Sen O-Sen OH . O-Sen O-Sen weak
B15 O-Sen O-Sen O-Sen OH O-Sen O-Sen weak
B16 O-Sen O-Sen OH O-Sen O-Sen O-Sen weak
B17 O-Sen OH O-Sen O-Sen O-Sen O-Sen weak
B18 OH O-Sen O-Sen O-Sen O-Sen O-Sen weak
B19 O-Sen O-Sen O-Sen O-Sen O-Sen O-Sen none
B20 O-Sen O-Sen OH OH OH O-Sen moderate
B21 O-Sen O-Sen OH OH O-Sen OH moderate
B22 O-Sen O-Sen OH O-Sen OH OH moderate
B23 O-Sen O-Sen O-Sen OH OH OH moderate
B24 O-Sen O-Sen OH OH OH OH moderate
B25 O-Sen OH OH OH OH O-Sen moderate
B26 OH O-Sen OH OH OH O-Sen moderate
B27 OH OH O-Sen OH OH O-Sen moderate
B28 OH OH OH O-Sen OH O-Sen moderate
B29 O-Sen OH OH OH O-Sen OH moderate
B30 OH O-Sen OH OH O-Sen OH moderate
B31 OH OH O-Sen OH O-Sen OH moderate
B32 OH OH OH O-Sen O-Sen OH moderate
Esterification of core compound E4A with 4-Pentenoyl chloride and isolation of the compounds with HPLC give the following compounds: wherein Pen = 4-Pentenoyl
R1 R2 R5 R8 R17 R18 Cytotoxicity activity
E4A OH OH OH OH OH OH none
C1 OH OH OH OH O-Pen OH moderate
C2 OH OH OH OH OH O-Pen moderate
C3 OH OH OH OH O-Pen O-Pen strong
C4 O-Pen OH OH OH O-Pen O-Pen moderate
C5 OH O-Pen OH OH O-Pen O-Pen moderate
C6 OH OH O-Pen OH O-Pen O-Pen moderate
C7 OH OH OH O-Pen O-Pen O-Pen moderate
C8 O-Pen O-Pen OH OH O-Pen O-Pen weak
C9 OH O-Pen O-Pen OH . O-Pen O-Pen weak
C10 OH OH O-Pen O-Pen O-Pen O-Pen weak
C1 1 O-Pen OH O-Pen OH O-Pen O-Pen weak
C12 OH O-Pen OH O-Pen O-Pen O-Pen weak
C13 O-Pen OH OH O-Pen O-Pen O-Pen weak
C14 OH O-Pen O-Pen OH O-Pen O-Pen weak
C15 O-Pen O-Pen O-Pen OH O-Pen O-Pen weak
C16 O-Pen O-Pen OH O-Pen O-Pen O-Pen weak
C17 O-Pen OH O-Pen O-Pen O-Pen O-Pen weak C18 OH O-Pen O-Pen O-Pen O-Pen O-Pen weak
C19 O-Pen O-Pen O-Pen O-Pen O-Pen O-Pen none
C20 O-Pen O-Pen OH OH OH O-Pen moderate
C21 O-Pen O-Pen OH OH O-Pen OH moderate
C22 O-Pen O-Pen OH O-Pen OH OH moderate
C23 O-Pen O-Pen O-Pen OH OH OH moderate
C24 O-Pen O-Pen OH OH OH OH moderate
C25 O-Pen OH OH OH OH O-Pen moderate
C26 OH O-Pen OH OH OH O-Pen moderate
C27 OH OH O-Pen OH OH O-Pen moderate
C28 OH OH OH O-Pen OH O-Pen moderate
C29 O-Pen OH OH OH O-Pen OH moderate
C30 OH O-Pen OH OH O-Pen OH moderate
C31 OH OH O-Pen OH O-Pen OH moderate
C32 OH OH OH O-Pen O-Pen OH moderate
Esterification of core compound E4A with Hexanoyl chloride and isolation of the compounds with HPLC give the following compounds: wherein Hex = Hexanoyl
R1 R2 R5 R8 R17 R18 Cytotoxicity activity
E4A OH OH OH OH OH OH none
D1 OH OH OH OH O-Hex OH moderate
D2 OH OH OH OH OH O-Hex moderate
D3 OH OH OH OH O-Hex O-Hex strong
D4 O-Hex OH OH OH O-Hex O-Hex moderate
D5 OH O-Hex OH OH O-Hex O-Hex moderate
D6 OH OH O-Hex OH O-Hex O-Hex moderate
D7 OH OH OH O-Hex O-Hex O-Hex moderate
D8 O-Hex O-Hex OH OH O-Hex O-Hex weak
D9 OH O-Hex O-Hex OH O-Hex O-Hex weak
D10 OH OH O-Hex O-Hex O-Hex O-Hex weak
D1 1 O-Hex OH O-Hex OH O-Hex O-Hex weak
D12 OH O-Hex OH O-Hex O-Hex O-Hex weak
D13 O-Hex OH OH O-Hex O-Hex O-Hex weak
D14 OH O-Hex O-Hex OH O-Hex O-Hex weak
D15 O-Hex O-Hex O-Hex OH O-Hex O-Hex weak
D16 O-Hex O-Hex OH O-Hex O-Hex O-Hex weak
D17 O-Hex OH O-Hex O-Hex O-Hex O-Hex weak
D18 OH O-Hex O-Hex O-Hex O-Hex O-Hex weak
D19 O-Hex O-Hex O-Hex O-Hex O-Hex O-Hex none
D20 O-Hex O-Hex OH OH OH O-Hex moderate
D21 O-Hex O-Hex OH OH O-Hex OH moderate
D22 O-Hex O-Hex OH O-Hex OH OH moderate
D23 O-Hex O-Hex O-Hex. OH OH OH moderate
D24 O-Hex O-Hex OH OH OH OH moderate
D25 O-Hex OH OH OH OH O-Hex moderate
D26 OH O-Hex OH OH OH O-Hex moderate
D27 OH OH O-Hex OH OH O-Hex moderate
D28 OH OH OH O-Hex OH O-Hex moderate
D29 O-Hex OH OH OH O-Hex OH moderate
D30 OH O-Hex OH OH O-Hex OH moderate D31 OH OH O-Hex OH O-Hex OH moderate
D32 OH OH OH O-Hex O-Hex OH moderate
Esterification of core compound E4A with 2-Ethylbutyryl chloride and isolation of the compounds with HPLC give the following compounds: wherein Eth= 2-Ethylbutyryl
Esterification of core compound E4A with Acetyl chloride (H) and isolation of the compounds with HPLC give the following compounds: wherein Acy = Acetyl
R1 R2 R5 R8 R17 R18 Cytotoxicity activity
E4A OH OH OH OH OH OH none
H1 OH OH OH OH O-Acy OH moderate
H2 OH OH OH OH OH O-Acy moderate
H3 OH OH OH OH O-Acy O-Acy strong
H4 O-Acy OH OH OH O-Acy O-Acy moderate
H5 OH O-Acy OH OH O-Acy O-Acy moderate H6 OH OH O-Acy OH O-Acy O-Acy moderate
H7 OH OH OH O-Acy O-Acy O-Acy moderate
H8 O-Acy O-Acy OH OH O-Acy O-Acy weak
H9 OH O-Acy O-Acy OH O-Acy O-Acy weak
H10 OH OH O-Acy O-Acy O-Acy O-Acy weak
H1 1 O-Acy OH O-Acy OH O-Acy O-Acy weak
H12 OH O-Acy OH O-Acy O-Acy O-Acy weak
H13 O-Acy OH OH O-Acy O-Acy O-Acy weak
H14 OH O-Acy O-Acy OH O-Acy O-Acy weak
H15 O-Acy O-Acy O-Acy OH O-Acy O-Acy weak
H16 O-Acy O-Acy OH O-Acy O-Acy O-Acy weak
H17 O-Acy OH O-Acy O-Acy O-Acy O-Acy weak
H18 OH O-Acy O-Acy O-Acy O-Acy O-Acy weak
H19 O-Acy O-Acy O-Acy O-Acy O-Acy O-Acy none
H20 O-Acy O-Acy OH OH OH O-Acy moderate
H21 O-Acy O-Acy OH OH O-Acy OH moderate
H22 O-Acy O-Acy OH O-Acy OH OH moderate
H23 O-Acy O-Acy O-Acy OH OH OH moderate
H24 O-Acy O-Acy OH OH OH OH moderate
H25 O-Acy OH OH OH OH O-Acy moderate
H26 OH O-Acy OH OH OH O-Acy moderate
H27 OH OH O-Acy OH OH O-Acy moderate
H28 OH OH OH O-Acy OH O-Acy moderate
H29 O-Acy OH OH OH O-Acy OH moderate
H30 OH O-Acy OH OH O-Acy OH moderate
H31 OH OH O-Acy OH O-Acy OH moderate
H32 OH OH OH O-Acy O-Acy OH moderate
Esterification of core compound E4A with CrotonoyI chloride and isolation of the compounds with HPLC give the following compounds: wherein Cro = CrotonoyI
R1 R2 R5 R8 R17 R18 Cytotoxicity activity
E4A OH OH OH OH OH OH none
I 1 OH OH OH OH O-Cro OH moderate
I 2 OH OH OH OH OH O-Cro moderate
I 3 OH OH OH OH O-Cro O-Cro strong
I 4 O-Cro OH OH OH O-Cro O-Cro moderate
I 5 OH O-Cro OH OH O-Cro O-Cro moderate
I 6 OH OH O-Cro OH O-Cro O-Cro moderate
I 7 OH OH OH O-Cro O-Cro O-Cro moderate
I 8 O-Cro O-Cro OH OH O-Cro O-Cro weak
I 9 OH O-Cro O-Cro OH O-Cro O-Cro weak
I 10 OH OH O-Cro O-Cro O-Cro O-Cro weak
I 1 1 O-Cro OH O-Cro OH O-Cro O-Cro weak
I 12 OH O-Cro OH O-Cro O-Cro O-Cro weak
I 13 O-Cro OH OH O-Cro O-Cro O-Cro weak
I 14 OH O-Cro O-Cro OH O-Cro O-Cro weak
I 15 O-Cro O-Cro O-Cro OH O-Cro O-Cro weak
I 16 O-Cro O-Cro OH O-Cro O-Cro O-Cro weak
I 17 O-Cro OH O-Cro O-Cro O-Cro O-Cro weak
I 18 OH O-Cro O-Cro O-Cro O-Cro O-Cro weak 1 19 O-Cro O-Cro O-Cro O-Cro O-Cro O-Cro none
I 20 O-Cro O-Cro OH OH OH O-Cro moderate
I 21 O-Cro O-Cro OH OH O-Cro OH moderate
I 22 O-Cro O-Cro OH O-Cro OH OH moderate
I 23 O-Cro O-Cro O-Cro OH OH OH moderate
I 24 O-Cro O-Cro OH OH OH OH moderate
I 25 O-Cro OH OH OH OH O-Cro moderate
I 26 OH O-Cro OH OH OH O-Cro moderate
I 27 OH OH O-Cro OH OH O-Cro moderate
I 28 OH OH OH O-Cro OH O-Cro moderate
I 29 O-Cro OH OH OH O-Cro OH moderate
I 30 OH O-Cro OH OH O-Cro OH moderate
I 31 OH OH O-Cro OH O-Cro OH moderate
I 32 OH OH OH O-Cro O-Cro OH moderate
Esterification of core compound E4A with CinnamoyI chloride and isolation of the compounds with HPLC give the following compounds; wherein Cin = CinnamoyI
R1 R2 R5 R8 R17 R18 Cytotoxicity activity
E4A OH OH OH OH OH OH none
J1 OH OH OH OH O-Cin OH moderate
J2 OH OH OH OH OH O-Cin moderate
J3 OH OH OH OH O-Cin O-Cin strong
J4 O-Cin OH OH OH O-Cin O-Cin moderate
J5 OH O-Cin OH OH O-Cin O-Cin moderate
J6 OH OH O-Cin OH O-Cin O-Cin moderate
J7 OH OH OH O-Cin O-Cin O-Cin moderate
J8 O-Cin O-Cin OH OH O-Cin O-Cin weak
J9 OH O-Cin O-Cin OH O-Cin O-Cin weak
J10 OH OH O-Cin O-Cin O-Cin O-Cin weak
J1 1 O-Cin OH O-Cin OH O-Cin O-Cin weak
J12 OH O-Cin OH O-Cin O-Cin O-Cin weak
J13 O-Cin OH OH O-Cin O-Cin O-Cin weak
J14 OH O-Cin O-Cin OH O-Cin O-Cin weak
J15 O-Cin O-Cin O-Cin OH O-Cin O-Cin weak
J16 O-Cin O-Cin OH O-Cin O-Cin O-Cin weak
J17 O-Cin OH O-Cin O-Cin O-Cin O-Cin weak
J18 OH O-Cin O-Cin O-Cin O-Cin O-Cin weak
J19 O-Cin O-Cin O-Cin O-Cin O-Cin O-Cin none
J20 O-Cin O-Cin OH OH OH O-Cin moderate
J21 O-Cin O-Cin OH OH O-Cin OH moderate
J22 O-Cin O-Cin OH O-Cin OH OH moderate
J23 O-Cin O-Cin O-Cin OH OH OH moderate
J24 O-Cin O-Cin OH OH OH OH moderate
J25 O-Cin OH OH OH OH O-Cin moderate
J26 OH O-Cin OH OH OH O-Cin moderate
J27 OH OH O-Cin OH OH O-Cin moderate
J28 OH OH OH O-Cin OH O-Cin moderate
J29 O-Cin OH OH OH O-Cin OH moderate
J30 OH O-Cin OH OH O-Cin OH moderate
J31 OH OH O-Cin OH O-Cin OH moderate J32 OH OH OH O-Cin O-Cin OH moderate
Esterification of core compound E4A with benzoyl chloride and isolation of the compounds with HPLC give the following compounds: wherein Ben = benzoyl
Esterification of core compound E4A with Propionyl chloride and isolation compounds with HPLC give the following compounds: wherein Ppi = Propionyl
R1 R2 R5 R8 R17 R18 Cytotoxicity activity
E4A OH OH OH OH OH OH none
K1 OH OH OH OH O-Ppi OH moderate
K2 OH OH OH OH OH O-Ppi moderate
K3 OH OH OH OH O-Ppi O-Ppi strong
K4 O-Ppi OH OH OH O-Ppi O-Ppi moderate
K5 OH O-Ppi OH OH O-Ppi O-Ppi moderate
K6 OH OH O-Ppi OH O-Ppi O-Ppi moderate K7 OH OH OH O-Ppi O-Ppi O-Ppi moderate
K8 O-Ppi O-Ppi OH OH O-Ppi O-Ppi weak
Κ9 OH O-Ppi O-Ppi OH O-Ppi O-Ppi weak
Κ10 OH OH O-Ppi O-Ppi O-Ppi O-Ppi weak
Κ1 1 O-Ppi OH O-Ppi OH O-Ppi O-Ppi weak
Κ12 OH O-Ppi OH O-Ppi O-Ppi O-Ppi weak
Κ13 O-Ppi OH OH O-Ppi O-Ppi O-Ppi weak
Κ14 OH O-Ppi O-Ppi OH O-Ppi O-Ppi weak
Κ15 O-Ppi O-Ppi O-Ppi OH O-Ppi O-Ppi weak
Κ16 O-Ppi O-Ppi OH O-Ppi O-Ppi O-Ppi weak
Κ17 O-Ppi OH O-Ppi O-Ppi O-Ppi O-Ppi weak
Κ18 OH O-Ppi O-Ppi O-Ppi O-Ppi O-Ppi weak
Κ19 O-Ppi O-Ppi O-Ppi O-Ppi O-Ppi O-Ppi none
Κ20 O-Ppi O-Ppi OH OH OH O-Ppi moderate
Κ21 O-Ppi O-Ppi OH OH O-Ppi OH moderate
Κ22 O-Ppi O-Ppi OH O-Ppi OH OH moderate
Κ23 O-Ppi O-Ppi O-Ppi OH OH OH moderate
Κ24 O-Ppi O-Ppi OH OH OH OH moderate
Κ25 O-Ppi OH OH OH OH O-Ppi moderate
Κ26 OH O-Ppi OH OH OH O-Ppi moderate
Κ27 OH OH O-Ppi OH OH O-Ppi moderate
Κ28 OH OH OH O-Ppi OH O-Ppi moderate
Κ29 O-Ppi OH OH OH O-Ppi OH moderate
Κ30 OH O-Ppi OH OH O-Ppi OH moderate
Κ31 OH OH O-Ppi OH O-Ppi OH moderate
Κ32 OH OH OH O-Ppi O-Ppi OH moderate
Esterification of core compound E4A with 2-propenoyl chloride and isolation of the compounds with HPLC give the following compounds: wherein Ppe = Propenoyl
R1 R2 R5 R8 R17 R18 Cytotoxicity activity
E4A OH OH OH OH OH OH none
K1 OH OH OH OH O-Ppe OH moderate
K2 OH OH OH OH OH O-Ppe moderate
K3 OH OH OH OH O-Ppe O-Ppe strong
K4 O-Ppe OH OH OH O-Ppe O-Ppe moderate
K5 OH O-Ppe OH OH O-Ppe O-Ppe moderate
K6 OH OH O-Ppe OH O-Ppe O-Ppe moderate
K7 OH OH OH O-Ppe O-Ppe O-Ppe moderate
K8 O-Ppe O-Ppe OH OH O-Ppe O-Ppe weak
K9 OH O-Ppe O-Ppe OH O-Ppe O-Ppe weak
K10 OH OH O-Ppe O-Ppe O-Ppe O-Ppe weak
K1 1 O-Ppe OH O-Ppe OH O-Ppe O-Ppe weak
K12 OH O-Ppe OH O-Ppe O-Ppe O-Ppe weak
K13 O-Ppe OH OH O-Ppe O-Ppe O-Ppe weak
K14 OH O-Ppe O-Ppe OH O-Ppe O-Ppe weak
K15 O-Ppe O-Ppe O-Ppe OH O-Ppe O-Ppe weak
K16 O-Ppe O-Ppe OH O-Ppe O-Ppe O-Ppe weak
K17 O-Ppe OH O-Ppe O-Ppe O-Ppe O-Ppe weak
K18 OH O-Ppe O-Ppe O-Ppe O-Ppe O-Ppe weak
K19 O-Ppe O-Ppe O-Ppe O-Ppe O-Ppe O-Ppe none K20 O-Ppe O-Ppe OH OH OH O-Ppe moderate
K21 O-Ppe O-Ppe OH OH O-Ppe OH moderate
K22 O-Ppe O-Ppe OH O-Ppe OH OH moderate
K23 O-Ppe O-Ppe O-Ppe OH OH OH moderate
K24 O-Ppe O-Ppe OH OH OH OH moderate
K25 O-Ppe OH OH OH OH O-Ppe moderate
K26 OH O-Ppe OH OH OH O-Ppe moderate
K27 OH OH O-Ppe OH OH O-Ppe moderate
K28 OH OH OH O-Ppe OH O-Ppe moderate
K29 O-Ppe OH OH OH O-Ppe OH moderate
K30 OH O-Ppe OH OH O-Ppe OH moderate
K31 OH OH O-Ppe OH O-Ppe OH moderate
K32 OH OH OH O-Ppe O-Ppe OH moderate
Esterification of core compound E4A with Isobutyryl chloride and isolation of the compounds with HPLC give the following compounds: wherein lso= Isobutyryl
R1 R2 R5 R8 R17 R18 Cytotoxicity activity
E4A OH OH OH OH OH OH none
K1 OH OH OH OH O-lso OH moderate
K2 OH OH OH OH OH O-lso moderate
K3 OH OH OH OH O-lso O-lso strong
K4 O-lso OH OH OH O-lso O-lso moderate
K5 OH O-lso OH OH O-lso O-lso moderate
K6 OH OH O-lso OH O-lso O-lso moderate
K7 OH OH OH O-lso O-lso O-lso moderate
K8 O-lso O-lso OH OH O-lso O-lso weak
K9 OH O-lso O-lso OH O-lso O-lso weak
K10 OH OH O-lso O-lso O-lso O-lso weak
K1 1 O-lso OH O-lso OH O-lso O-lso weak
K12 OH O-lso OH O-lso O-lso O-lso weak
K13 O-lso OH OH O-lso O-lso O-lso weak
K14 OH O-lso O-lso OH O-lso O-lso weak
K15 O-lso O-lso O-lso OH O-lso O-lso weak
K16 O-lso O-lso OH O-lso O-lso O-lso weak
K17 O-lso OH O-lso O-lso O-lso O-lso weak
K18 OH O-lso O-lso O-lso O-lso O-lso weak
K19 O-lso O-lso O-lso O-lso O-lso O-lso none
K20 O-lso O-lso OH OH OH O-lso moderate
K21 O-lso O-lso OH OH O-lso OH moderate
K22 O-lso O-lso OH O-lso OH OH moderate
K23 O-lso O-lso O-lso OH OH OH moderate
K24 O-lso O-lso OH OH OH OH moderate
K25 O-lso OH OH OH OH O-lso moderate
K26 OH O-lso OH OH OH O-lso moderate
K27 OH OH O-lso OH OH O-lso moderate
K28 OH OH OH O-lso OH O-lso moderate
K29 O-lso OH OH OH O-lso OH moderate
K30 OH O-lso OH OH O-lso OH moderate
K31 OH OH O-lso OH O-lso OH moderate
K32 OH OH OH O-lso O-lso OH moderate Esterification of core compound E4A with Butyryl chloride and isolation of the compounds with HPLC give the following compounds: wherein But = Butyryl
Esterification of core compound E4A with (2E)-2-pentenoyl chloride and isolation of the compounds with HPLC give the following compounds: wherein 2pe = 2-pent
R1 R2 R5 R8 R17 R18 Cytotoxicity activity
E4A OH OH OH OH OH OH none
K1 OH OH OH OH 0-2pe OH moderate
K2 OH OH OH OH OH 0-2pe moderate
K3 OH OH OH OH 0-2pe 0-2pe strong
K4 0-2pe OH OH OH 0-2pe 0-2pe moderate
K5 OH 0-2pe OH OH 0-2pe 0-2pe moderate
K6 OH OH 0-2pe OH 0-2pe 0-2pe moderate
K7 OH OH OH 0-2pe 0-2pe 0-2pe moderate K8 0-2pe 0-2pe OH OH 0-2pe 0-2pe weak
K9 OH 0-2pe 0-2pe OH 0-2pe 0-2pe weak
Κ10 OH OH 0-2pe 0-2pe 0-2pe 0-2pe weak
Κ1 1 0-2pe OH 0-2pe OH 0-2pe 0-2pe weak
Κ12 OH 0-2pe OH 0-2pe 0-2pe 0-2pe weak
Κ13 0-2pe OH OH 0-2pe 0-2pe 0-2pe weak
Κ14 OH 0-2pe 0-2pe OH 0-2pe 0-2pe weak
Κ15 0-2pe 0-2pe 0-2pe OH 0-2pe 0-2pe weak
Κ16 0-2pe 0-2pe OH 0-2pe 0-2pe 0-2pe weak
Κ17 0-2pe OH 0-2pe 0-2pe 0-2pe 0-2pe weak
Κ18 OH 0-2pe 0-2pe 0-2pe 0-2pe 0-2pe weak
Κ19 0-2pe 0-2pe 0-2pe 0-2pe 0-2pe 0-2pe none
Κ20 0-2pe 0-2pe OH OH OH 0-2pe moderate
Κ21 0-2pe 0-2pe OH OH 0-2pe OH moderate
Κ22 0-2pe 0-2pe OH 0-2pe OH OH moderate
Κ23 0-2pe 0-2pe 0-2pe OH OH OH moderate
Κ24 0-2pe 0-2pe OH OH OH OH moderate
Κ25 0-2pe OH OH OH OH 0-2pe moderate
Κ26 OH 0-2pe OH OH OH 0-2pe moderate
Κ27 OH OH 0-2pe OH OH 0-2pe moderate
Κ28 OH OH OH 0-2pe OH 0-2pe moderate
Κ29 0-2pe OH OH OH 0-2pe OH moderate
Κ30 OH 0-2pe OH OH 0-2pe OH moderate
Κ31 OH OH 0-2pe OH 0-2pe OH moderate
Κ32 OH OH OH 0-2pe 0-2pe OH moderate
Esterification of core compound E4A with OctanoyI chloride and isolation of the compounds with HPLC give the following compounds: wherein Oct = OctanoyI
R1 R2 R5 R8 R17 R18 Cytotoxicity activity
E4A OH OH OH OH OH OH none
K1 OH OH . OH OH O-Oct OH moderate
K2 OH OH OH OH OH O-Oct moderate
K3 OH OH OH OH O-Oct O-Oct strong
K4 O-Oct OH OH OH O-Oct O-Oct moderate
K5 OH O-Oct OH OH O-Oct O-Oct moderate
K6 OH OH O-Oct OH O-Oct O-Oct moderate
K7 OH OH OH O-Oct O-Oct O-Oct moderate
K8 O-Oct O-Oct OH OH O-Oct O-Oct weak
K9 OH O-Oct O-Oct OH O-Oct O-Oct weak
K10 OH OH O-Oct O-Oct O-Oct O-Oct weak
K1 1 O-Oct OH O-Oct OH O-Oct O-Oct weak
K12 OH O-Oct OH O-Oct O-Oct O-Oct weak
K13 O-Oct OH OH O-Oct O-Oct O-Oct weak
K14 OH O-Oct O-Oct OH O-Oct O-Oct weak
K15 O-Oct O-Oct O-Oct OH O-Oct O-Oct weak
K16 O-Oct O-Oct OH O-Oct O-Oct O-Oct weak
K17 O-Oct OH O-Oct O-Oct O-Oct O-Oct weak
K18 OH O-Oct O-Oct O-Oct O-Oct O-Oct weak
K19 O-Oct O-Oct O-Oct O-Oct O-Oct O-Oct none
K20 O-Oct O-Oct OH OH OH O-Oct moderate K21 O-Oct O-Oct OH OH O-Oct OH moderate
K22 O-Oct O-Oct OH O-Oct OH OH moderate
K23 O-Oct O-Oct O-Oct OH OH OH moderate
K24 O-Oct O-Oct OH OH OH OH moderate
K25 O-Oct OH OH OH OH O-Oct moderate
K26 OH O-Oct OH OH OH O-Oct moderate
K27 OH OH O-Oct OH OH O-Oct moderate
K28 OH OH OH O-Oct OH O-Oct moderate
K29 O-Oct OH OH OH O-Oct OH moderate
K30 OH O-Oct OH OH O-Oct OH moderate
K31 OH OH O-Oct OH O-Oct OH moderate
K32 OH OH OH O-Oct O-Oct OH moderate
Esterification of core compound E4A with DecanoyI chloride and isolation of the compounds with HPLC give the following compounds: wherein Dec = DecanoyI
Esterification of core compound E4A with MyristoyI chloride and isolation of the compounds with HPLC give the following compounds: wherein Myr = MyristoyI
Esterification of E4A-Tig-N with senecioyi chloride and isolation of the compounds with HPLC give the following compounds:
Esterification of E4A-Tig-N with CrotonoyI chloride and isolation of the compounds with
HPLC give the following compounds:
Esterification of E4A-Tig-N with Acetyl chloride and isolation of the compounds with HPLC give the following compounds:
Esterification of E4A-Tig-N with 4-Pentenoyl chloride and isolation of the compounds with HPLC give the following compounds:
Esterification of E4A-Tig-N with Hexanoly chloride and isolation of the compounds with
HPLC give the following compounds:
Esterification of E4A-Tig-N with Cinnamoyl chloride and isolation of the compounds with
HPLC give the following compounds: R1 R2 R5 R8 R17 R18 Cytotoxicity activity
E4A-Tig-N OH OH OH OH O-Tig OH moderate
Tiq-Cin-1 OH OH OH OH O-Tig O-Cin strong
Tiq-Cin-2 O-Cin OH OH OH O-Tig O-Cin moderate
Tig-Cin-3 OH O-Cin OH OH O-Tig O-Cin moderate
Tig-Cin-4 OH OH O-Cin OH O-Tig O-Cin moderate
Tig-Cin-5 O-Cin OH OH OH O-Tig OH moderate
Tig-Cin-6 OH O-Cin OH OH O-Tig OH moderate
Esterification of E4A-Tig-N with AngeloyI chloride and isolation of the compounds with HPLC give the following compounds:
Esterification of E4A-Tig-N with 2-Ethylbutyryl chloride and isolation of the compounds with HPLC give the following compounds:
Esterification of E4A-Tig-R with senecioyi chloride and isolation of the compounds with HPLC give the following compounds:
Esterification of E4A-Tig-R with Crotonoyl chloride and isolation of the compounds with HPLC give the following compounds:
R1 R2 R5 R8 R17 R18 Cytotoxicity activity
E4A-Tiq-R OH OH OH OH O-Tig O-Tig strong
Tig-R-Cro-1 O-Cro O-Cro OH OH O-Tig O-Tig weak
Tiq-R-Cro-2 O-Cro OH OH OH O-Tig O-Tig moderate Tig-R-Cro-3 OH O-Cro OH OH O-Tig O-Tig moderate
Tig-R-Cro-4 OH OH O-Cro OH O-Tig O-Tig moderate
Tiq-R-Cro-5 O-Cro OH O-Cro OH O-Tig O-Tig weak
Tig-R-Cro-6 OH O-Cro O-Cro OH O-Tig O-Tig weak
Esterification of E4A-Tig-R with Acetyl chloride and isolation of the compounds with
HPLC give the following compounds:
Esterification of E4A-Tig-R with 4-Pentenoyl chloride and isolation of the compounds with HPLC give the following compounds:
Esterification of E4A-Tig-R with Hexanoly chloride and isolation of the compounds with
HPLC give the following compounds:
Esterification of E4A-Tig-R with Cinnamoyl chloride and isolation of the compounds with
HPLC give the following compounds:
R1 R2 R5 R8 R17 R18 Cytotoxicity activity
E4A-Tig-R OH OH OH OH O-Tig O-Tig strong
Tig-R-Cin-1 O-Cin O-Cin OH OH O-Tig O-Tig weak
Tig-R-Cin-2 O-Cin OH OH OH O-Tig O-Tig moderate
Tig-R-Cin-3 OH O-Cin OH OH O-Tig O-Tig moderate
Tig-R-Cin-4 OH OH O-Cin OH O-Tig O-Tig moderate Tiq-R-Cin-5 O-Cin OH O-Cin OH O-Tig O-Tig weak
Tig-R-Cin-6 OH O-Cin O-Cin OH O-Tig O-Tig weak
Esterification of E4A-Tig-R with Angeloyl chloride and isolation of the compounds with
HPLC give the following compounds:
Esterification of E4A-Tig-R with 2-Ethylbutyryl chloride and isolation of the compounds with HPLC give the following compounds:
Esterification of compound (A), (B), (C), (D1 ), (D2), (E), (F), (G), (H1 ), (H2), terpene, isoprene, triterpenes, hydroxylated triterpenes, with acyl halide, wherein the halide comprise chloride, bromide, fluoride and iodide, wherein the acyl halide comprise acyl chloride, wherein acyl chloride comprise tigloyl chloride, angeloyl chloride, acetyl chloride, crotonoyl chloride, 3,3-dimethylartyloyl chloride, senecioyl chloride, cinnamoyl chloride, pentenoyl chloride, hexanoyl chloride, benzoyl chloride, ethylbutyryl chloride, propionyl chloride, 2-propenoyl chloride, isobutyryl chloride, butyryl chloride, (2E)-2- pentenoyl chloride, 4-Pentenoyl chloride, 5-hexenoyl chloride, heptanoyl chloride, octanoyl chloride, nonanoyl chloride, decanoyl chloride, Lauroyl chloride, myristoyl chloride, oleoyl chloride. The compounds vary in composition when the time or temperature of the reaction is changed. The peaks, fractions and compounds are selected according to the activities of times studies arid the changes of peaks. The compounds having strong to weak activities are selected and isolated. The anti cancer activities (Cytotoxic Assay) are the MTT studies of bone (U20S), lung (H460), bladder(HTB-9), ovary (ES2), colon (HCT1 16), pancreas (Capan), ovary (OVCAR3), prostate (DU145), skin (SK-Mel-5), mouth (KB), kidney (A498), breast (MCF-7), liver (HepG2), brain (T98G), luekemia (K562), cervix (HeLa). The active esterification products are purified with HPLC. The reaction product of mixtures and individual compounds are tested with MTT Cytotoxic Assay. Details of method are in Experiment 3 of the present application. A second esterification of compound can be selected from the above experiment results to produce new active compounds. A partial esterification compound is selected from the above experiments to perform a second or repeated with a third esterification with different acyl chloride in order to produce new active compounds with the experiments in the present application. A method is 1 ) Dissolving core compound or triterpenes core, hydroxylated triterpenes core, in pyridine; 2) Adding acyl halide or acyl chloride; 3, The mixture is stirred for length of time including 5 sec, 10 sec, 20 sec, 30 sec, 40 sec, 1 min, 2 min, 5 min, 10 min, 30 min, 1 hr, 2 hr, 18 hr, 2 days or 3 days at different temperature; 4) At the end of reaction, aqueous solution of acid or weak base, or water is added to the reaction mixture; 5) The solution is then extracted of ethyl acetate and ethyl acetate is removed by evaporation and lyophilization; 6) Dissolving the reaction product in acetonitrile with Trifluoroacetic acid or DMSO; 7) Testing the reaction product of mixtures and individual fractions with MTT cytotoxic assay; 8) Selecting the HPLC fractions for isolation is according to the cytotoxic activity of the reaction product obtained at a specific reaction time; 10) Purifiing the active esterification products with HPLC; 1 1) Collecting the products; 12) Testing the products; wherein the core compound is terpene, isoprene, or triterpene core or hydroxylated triterpenes core; wherein the core compound was dissolved in pyridine; wherein the acyl chloride including Tigloyl chloride, angeloyl chloride, Acetyl chloride, Crotonoyl chloride, 3,3-Dimethylartyloyl chloride, senecioyl chloride, Cinnamoyl chloride, Pentenoyl chloride, Hexanoyl chloride, benzoyl chloride, Ethylbutyryl chloride, Propionyl chloride, 2-Propenoyl chloride, Isobutyryl chloride, Butyryl chloride, (2E)-2-pentenoyl chloride, 4-Pentenoyl chloride, 5-Hexenoyl chloride, Heptanoyl chloride, Octanoyl chloride, Nonanoyl chloride, Decanoyl chloride, Lauroyl chloride, Myristoyl chloride, and Oleoyl chloride; wherein the reaction time for the mixture is stirred for 5 sec, 10 sec, 20 sec, 30 sec, 40 sec, 1 min, 2 min, 5 min, 10 min, 30 min, 1 hr, 2 hr, 18 hr, 2 days or 3 days; wherein the temperature is OC, 25C, 50 or 75C temperature; wherein the acid including HCI or the base including NaHC03 is added to the reaction mixture; wherein the solution is then extracted 3 times with ethyl acetate and lyophilization; wherein the reaction product is dissolved in 80% acetonitrile - 0.005% Trifluoroacetic acid or DMSO; wherein selecting the HPLC fractions for isolation is according to the cytotoxic activity of the reaction product obtained at a reaction time of 5 sec, 10 sec, 20 sec, 30 sec, 40 sec, 1 min, 2 min, 5 min, 10 min, 30 min, 1 hr, 2 hr, 18 hr, 2 days or 3 days. In an embodiment, the reaction time may be ove 3 days. In an embodiment, the experiment may be performed under 0C. In an embodiment, the experiment may be performed over 75C.
The anti-cancer activities of Tig-R compound: IC50 of bone (U20S) is 4.5 ug/ml, lung (H460) is 4.8 ug/ml, bladder(HTB-9) is 2.5 ug/ml, ovary (ES2) is 2.8 ug/ml, colon (HCT1 16) is 5.2 ug/ml, pancreas (Capan) 2.4 ug/ml, ovary(OVCAR3) is 5.8, prostate (DU145) is 3.6 ug/ml, skin (SK-Mel-5) is 5.1 ug/ml, mouth (KB) is 3 ug/ml, kidney (A498) is 3.5 ug/ml, breast (MCF-7) is 4.5 ug/ml, liver (HepG2) is 6 ug/ml, brain (T98G) is 8 ug/ml), leukemia (K562) is 2 ug/ml, cervix (HeLa) is 5 ug/ml.
The anti-cancer activities of Tig-V compound: IC50 of bone (U20S) is 7 ug/ml, lung (H460) is 6.8 ug/ml, bladder(HTB-9) is 4 ug/ml, ovary (ES2) is 2 ug/ml, colon (HCT1 16) is 8 ug/ml, pancreas (Capan) 5 ug/ml, ovary(OVCAR3) is 9, prostate (DU145) is 4 ug/ml, skin (SK-Mel-5) is 6ug/ml, mouth (KB) is 4.5 ug/ml, kidney (A498) is 4.8 ug/ml, breast (MCF-7) is 9 ug/ml, liver (HepG2) is 12 ug/ml, brain (T98G) is 14 ug/ml), leukemia (K562) is 4 ug/ml, cervix (HeLa) is 7 ug/ml. The anti-cancer activities of Tig-N compound: IC50 of bone (U20S) is 15 ug/ml, lung (H460) is 13 ug/ml, bladder(HTB-9) is 7.5 ug/ml, ovary (ES2) is 9 ug/ml, colon (HCT1 16) is 15 ug/ml, pancreas (Capan) 8 ug/ml, ovary(OVCAR3) is 18, prostate (DU145) is 4.8 ug/ml, skin (SK-Mel-5) is 15 ug/ml, mouth (KB) is 9 ug/ml, kidney (A498) is 11 ug/ml, breast (MCF-7) is 13 ug/ml, liver (HepG2) is 18 ug/ml, brain (T98G) is 19 ug/ml), leukemia (K562) is 6 ug/ml, cervix (HeLa) is 15 ug/ml.
The anti-cancer activities of Tig-Q compound: IC50 of bone (U20S) is 20 ug/ml, lung (H460) is 18 ug/ml, bladder(.HTB-9) is 10 ug/ml, ovary (ES2) is 12 ug/ml, colon (HCT116) is 22 ug/ml, pancreas (Capan) 9 ug/ml, ovary(OVCAR3) is 23, prostate (DU145) is 15 ug/ml, skin (SK-Mel-5) is 20ug/ml, mouth (KB) is 12 ug/ml, kidney (A498) is 13 ug/ml, breast (MCF-7) is 18 ug/ml, liver (HepG2) is 24 ug/ml, brain (T98G) is 29 ug/ml), leukemia (K562) is 6 ug/ml, cervix (HeLa) is 20 ug/ml.
The anti-cancer activities of Tig-T compound: IC50 of bone (U20S) is 20 ug/ml, lung (H460) is 21 ug/ml, bladder(HTB-9) is 12 ug/ml, ovary (ES2) is 14 ug/ml, colon (HCT116) is 23 ug/ml, pancreas (Capan) 10 ug/ml, ovary(OVCAR3) is 25, prostate (DU145) is 16 ug/ml, skin (SK-Mel-5) is 22ug/ml, mouth (KB) is 13 ug/ml, kidney (A498) is 15 ug/ml, breast (MCF-7) is 20 ug/ml, liver (HepG2) is 26 ug/ml, brain (T98G) is 26 ug/ml), leukemia (K562) is 9 ug/ml, cervix (HeLa) is 18 ug/ml. The anti-cancer activities of Tig-S compound: IC50 of bone (U20S) is 5.2 ug/ml, lung (H460) is 5.6 ug/ml, bladder(HTB-9) is 3.5 ug/ml, ovary (ES2) is 0.1 ug/ml, colon (HCT1 16) is 6.6 ug/ml, pancreas (Capan) 2.9 ug/ml, ovary(OVCAR3) is 6.5, prostate (DU145) is 4.3 ug/ml, skin (SK-Mel-5) is 5.8ug/ml, mouth (KB) is 4 ug/ml, kidney (A498) is 4.8 ug/ml, breast (MCF-7) is 6.3 ug/ml, liver (HepG2) is 8.5 ug/ml, brain (T98G) is 9 ug/ml), leukemia (K562) is 4.3 ug/ml, cervix (HeLa) is 7 ug/ml.
The anti-cancer activities of Tig-U compound: IC50 of bone (U20S) is 23 ug/ml, lung (H460) is 19 ug/ml, bladder(HTB-9) is 15 ug/ml, ovary (ES2) is 17 ug/ml, colon (HCT1 16) is 26 ug/ml, pancreas (Capan) 9 ug/ml, ovary(OVCAR3) is 27, prostate (DU145) is 15 ug/ml, skin (SK-Mel-5) is 24ug/ml, mouth (KB) is 16 ug/ml, kidney (A498) is 18 ug/ml, breast (MCF-7) is 25 ug/ml, liver (HepG2) is 23 ug/ml, brain (T98G) is 22 ug/ml), leukemia (K562) is 10 ug/ml, cervix (HeLa) is 17 ug/ml.
The IC50 of Tig-R in normal human fibroblast cells (WI38) is about 10-15 ug/ml. This IC50 value is 3 times higher than those in ovary ES2 (2.8 ug/ml) and lung (H460) is 4.8 ug/ml.
Swiss3T3 cells are mouse normal fibroblast which were used in this experiment to compare with ES2 (human ovarian cancer) in Tig-R cytotoxicity determination. The preliminary results indicate that the IC50 of Tig-R in SW3T3 cells is above 20 ug/ml while the corresponding IC50 in ES2 cells is about 2.8 ug/ml.
This invention provides compounds, methods, or uses of a compound for the manufacture of a medicament, or uses of a compound for medicament selected from formula (2A), for treating cancer, inhibiting cancer growth, inhibiting cancer invasion, inhibiting cancer metastasis, modulating cell adhesion, modulating cell attachment, wherein the compounds with reduced heamolytic character/characteristic, using compounds selected from the following:
R1 , R2, R3, R4, R5, R8, R9, R10, R1 1 , R12, R13, R14, R15 are independently selected from the group of hydrogen, hydroxyl, methyl, O-angeloyl, O-tigloyl, O-senecioyl, O- acetyl, O-Crotonoyl, 0-3,3-Dimethylartyloyl, O-Cinnamoyl, O-Pentenoyl, O-HexanoyI, O-benzoyl, O-Ethylbutyryl, O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O- benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O-alkenylcarbonyl, O- ethanoyl, O-propanoyl, O-propenoyl, O-butanoyl, O-butenoyl, O-pentanoyl, O-hexenoyl, O-heptanoyl, O-heptenoyl, O-octanoyl, O-octenoyl, O-nonanoyl, O-nonenoyl, O- decanoyl, O-decenoyl, O-propionyl, O-2-propenoyl, O-2-butenoyl, O-lsobutyryl, 0-2- methylpropanoyl, O-2-ethylbutyryl, O-ethylbutanoyl, O-2-ethylbutanoyl, O-butyryl, O- (E)-2,3-Dimethylacryloyl, 0-(E)-2-Methylcrotonoyl, O-3-c/s- ethyl-methacryloyl, 0-3- Methyl-2-butenoyl, O-3-Methylcrotonoyl, O-4-Pentenoyl, 0-(2E)-2-pentenoyl, O- Caproyl, O-5-Hexenoyl, O-Capryloyl, O-Lauroyl, O-Dodecanoyl, O-Myristoyl, O- Tetradecanoyl, O-Oleoyl, 0-C(2-18) Acyl, CH20-angeloyl, CH20-tigloyl, CH20- senecioyl, CH20-acetyl, CH20-Crotonoyl, CH20-3,3-Dimethylartyloyl, CH20- Cinnamoyl, CH20-Pentenoyl, CH20-Hexanoyl, CH20-benzoyl, CH20-Ethylbutyryl, CH3, CH20H, CH20-alkyl, CH20-dibenzoyl, CH20-benzoyl, CH20-alkanoyl, CH20- alkenoyl, CH20-benzoyl alkyl substituted O-alkanoyl, CH20-alkanoyl substituted phenyl, CH20-alkenoyl substituted phenyl, CH20-aryl, CH20-acyl, CH20-heterocylic, CH20- heteroraryl, CH20-alkenylcarbonyl, CH20-ethanoyl, CH20-propanoyl, CH20-propenoyl, CH20-butanoyl, CH20-butenoyl, CH20-pentanoyl, CH20-hexenoyl, CH20-heptanoyl, CH20-heptenoyl, CH20-octanoyl, CH20-octenoyl, CH20-nonanoyl, CH20-nonenoyl, CH20-decanoyl, CH20-decenoyl, CH20-propionyl, CH20-2-propenoyl, CH20-2- butenoyl, CH20-lsobutyryl, CH20-2-methylpropanoyl, CH20-2-ethylbutyryl, CH20- ethylbutanoyl, CH20-2-ethylbutanoyl, CH20-butyryl, CH20-(E)-2,3-Dimethylacryloyl, CH20-(E)-2-Methylcrotonoyl, CH20-3-c/ ' s-Methyl-methacryloyl, CH20-3-Methyl-2- butenoyl, CH20-3-Methylcrotonoyl, CH20-4-Pentenoyl, CH20-(2E)-2-pentenoyl, CH20-Caproyl, CH20-5-Hexenoyl, CH20-Capryloyl, CH20-Lauroyl, CH20- Dodecanoyl, CH20-Myristoyl, CH20-Tetradecanoyl, CH20-Oleoyl, CH20-C(2-18) Acyl, alkane, alkene and sugar moiety or derivatives thereof; or wherein the structure (2A) comprises at least 2 groups selected from O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, 0-3,3-Dimethylartyloyl, O-Cinnamoyl, O-Pentenoyl, O-Hexanoyl, O- benzoyl, O-Ethylbutyryl, O-alkyl, O-dibenzoyl, O-benzoyI, O-alkanoyl, O-alkenoyl, O- benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O-alkenylcarbonyl, O- ethanoyl, O-propanoyl, O-propenoyl, O-butanoyl, O-butenoyl, O-pentanoyl, O-hexenoyl, O-heptanoyl, O-heptenoyl, O-octanoyl, O-octenoyl, O-nonanoyl, O-nonenoyl, O- decanoyl, O-decenoyl, O-propionyl, O-2-propenoyl, O-2-butenoyl, O-lsobutyryl, 0-2- methylpropanoyl, O-2-ethylbutyryl, O-ethylbutanoyl, O-2-ethylbutanoyl, O-butyryl, O-(E)- 2,3-Dimethylacryloyl, 0-(E)-2-Methylcrotonoyl, O-3-c/s-Methyl-methacryloyl, 0-3- ethyl-2-butenoyl, O-3-Methylcrotonoyl, O-4-Pentenoyl, 0-(2E)-2-pentenoyl, O- Caproyl, O-5-Hexenoyl, O-Capryloyl, O-Lauroyl, O-Dodecanoyl, O-Myristoyl, O- Tetradecanoyl, O-Oleoyl, 0-C(2-18) Acyl; or wherein R1 and R2 are selected from O- angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, 0-3,3-Dimethylartyloyl, O- Cinnamoyl, O-Pentenoyl, O-Hexanoyl, O-benzoyI, O-Ethylbutyryl, O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyI alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O- heteroraryl, O-alkenylcarbonyl, O-ethanoyl, O-propanoyl, O-propenoyl, O-butanoyl, O- butenoyl, O-pentanoyl, O-hexenoyl, O-heptanoyl, O-heptenoyl, O-octanoyl, O-octenoyl, O-nonanoyl, O-nonenoyl, O-decanoyl, O-decenoyl, O-propionyl, O-2-propenoyl, 0-2- butenoyl, O-lsobutyryl, O-2-methylpropanoyl, O-2-ethylbutyryl, O-ethylbutanoyl, 0-2- ethylbutanoyl, O-butyryl, O- (E)-2,3-Dimethylacryloyl, 0-(E)-2-Methylcrotonoyl, O-3-c s- Methyl-methacryloyl, 0-3- ethyl-2-butenoyl, O-3-Methylcrotonoyl, O-4-Pentenoyl, O- (2E)-2-pentenoyl, O-Caproyl, O-5-Hexenoyl, O-Capryloyl, O-Lauroyl, O-Dodecanoyl, O- MyristoyI, O-Tetradecanoyl, O-Oleoyl, 0-C(2-18) Acyl; or wherein R4 and R10 are selected from CH20-angeloyl, CH20-tigloyl, CH20-senecioyl, CH20-acetyl, CH20- Crotonoyl, CH20-3,3-Dimethylartyloyl, CH20-Cinnamoyl, CH20-Peritenoyl, CH20- Hexanoyl, CH20-benzoyl, CH20-Ethylbutyryl, CH3, CH20H, CH20-alkyl, CH20- dibenzoyl, CH20-benzoyl, CH20-alkanoyl, CH20-alkenoyl, CH20-benzoyl alkyl substituted O-alkanoyl, CH20-alkanoyl substituted phenyl, CH20-alkenoyl substituted phenyl, CH20-aryl, CH20-acyl, CH20-heterocylic, CH20-heteroraryl, CH20- alkenylcarbonyl, CH20-ethanoyl, CH20-propanoyl, CH20-propenoyl, CH20-butanoyl, CH20-butenoyl, CH20-pentanoyl, CH20-hexenoyl, CH20-heptanoyl, CH20-heptenoyl, CH20-octanoyl, CH20-octenoyl, CH20-nonanoyl, CH20-nonenoyl, CH20-decanoyl, CH20-decenoyl, CH20-propionyl, CH20-2-propenoyl, CH20-2-butenoyl, CH20- Isobutyryl, CH20-2-methylpropanoyl, CH20-2-ethylbutyryl, CH20-ethylbutanoyl, CH20-2-ethylbutanoyl, CH20-butyryl, CH20-(E)-2,3-Dimethylacryloyl, . CH20-(E)-2- Methylcrotonoyl, CH20-3-c/s-Methyl-methacryloyl, CH20-3-Methyl-2-butenoyl, CH20- 3-Methylcrotonoyl, CH20-4-Pentenoyl, CH20-(2E)-2-pentenoyl, CH20-Caproyl, CH20- 5-Hexenoyl, CH20-Capryloyl, CH20-Lauroyl, CH20-Dodecanoyl, CH20-Myristoyl, CH20-Tetradecanoyl, CH20-Oleoyl, CH20-C(2-18) Acyl. In an embodiment, wherein the R1 and R2 are attached OH. In an embodiment, wherein R4, R10 are attached a CH20-angeloyl, CH20-tigloyl, CH20-senecioyl, CH20-acetyl, CH20-Crotonoyl, CH20- 3,3-Dimethylartyloyl, CH20-Cinnamoyl, CH20-Pentenoyl, CH20-Hexanoyl, CH20- benzoyl, or CH20-Ethylbutyryl. In an embodiment, wherein the R3 and R8 is hydrogen or hydroxyl, In an embodiment, wherein the R9, R1 1 , R12, R13, R14, R15 are independently attached with a methyl. In an embodiment, wherein R4 represents CH3, CHO, CH 2 R6 or COR6, wherein R6 is selected from hydroxyl, O-angeloyl, O-tigloyl, O- senecioyl, O-acetyl, O-Crotonoyl, 0-3,3-Dimethylartyloyl, O-Cinnamoyl, O-Pentenoyl, O-Hexanoyl, O-Ethylbutyryl, O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O-alkenylcarbonyl , O- ethanoyl, O-propanoyl, O-propenoyl, O-butanoyl, O-butenoyl, O-pentanoyl, O-hexenoyl, O-heptanoyl, O-heptenoyl, O-octanoyl, O-octenoyl, O-nonanoyl, O-nonenoyl, O- decanoyl, O-decenoyl, O-propionyl, O-2-propenoyl, O-2-butenoyl, O-lsobutyryl, 0-2- methylpropanoyl, O-2-ethylbutyryl, O-ethylbutanoyl, O-2-ethylbutanoyl, O-butyryl, O- (E)-2,3-Dimethylacryloyl, 0-(E)-2-Methylcrotonoyl, O-3-c/s-Methyl-methacryloyl, 0-3- Methyl-2-butenoyl, O-3-Methylcrotonoyl, O-4-Pentenoyl, 0-(2E)-2-pentenoyl, O- Caproyl, O-5-Hexenoyl, O-Capryloyl, O-Lauroyl, O-Dodecanoyl, O-Myristoyl, O- Tetradecanoyl, O-Oleoyl, 0-C(2-18) Acyl and derivatives thereof; In an embodiment, wherein R3 is H or OH; In an embodiment, wherein R8 is H or OH; In an embodiment, wherein R16 is H, CH3, OH ,or R4 and R16 may together form -CH2-X-, CH(OH)-X- or C(=0)-X-, wherein the -X- may be O or NH or S; wherein when the C12-13 of ring 3 of the triterpene has a double bond then R16 is absent. In an embodiment, wherein R10 represents CH3, CHO, or CH 2 R6, wherein R6 is selected from hydroxyl, O-angeloyl, O- tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, 0-3,3-Dimethylartyloyl, O-Cinnamoyl, O- Pentenoyl, O-Hexanoyl, O-benzoyl, O-Ethylbutyryl, O-alkyl, O-dibenzoyl, O-benzoyl, O- alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O- alkenylcarbonyl, O-ethanoyl, O-propanoyl, O-propenoyl, O-butanoyl, O-butenoyl, O- pentanoyl, O-hexenoyl, O-heptanoyl, O-heptenoyl, O-octanoyl, O-octenoyl, O- nonanoyl, O-nonenoyl, O-decanoyl, O-decenoyl, O-propionyl, O-2-propenoyl, 0-2- butenoyl, O-lsobutyryl, O-2-methylpropanoyl, O-2-ethylbutyryl, O-ethylbutanoyl, 0-2- ethylbutanoyl, O-butyryl, O- (E)-2,3-Dimethylacryloyl, 0-(E)-2-Methylcrotonoyl, O-3-c/s- Methyl-methacryloyl, 0-3-Methyl-2-butenoyl, O-3-Methylcrotonoyl, O-4-Pentenoyl, O- (2E)-2-pentenoyl, O-Caproyl, O-5-Hexenoyl, O-Capryloyl, O-Lauroyl, O-Dodecanoyl, O- MyristoyI, O-TetradecanoyI, O-Oleoyl, 0-0(2-18) Acyl and derivatives thereof; In an embodiment, wherein R5 is a hydrogen, hydroxyl, heterocyclic or O-sugar moiety(ies), wherein the sugar moiety(ies) is/are selected from a group consisting of glucose, galactose, rhamnose, arabinose, xylose, fucose, allose, altrose, gulose, idose, lyxose, mannose, psicose, ribose, sorbose, tagatose, talose, fructose, alduronic acid, glucuronic acid, galacturonic acid, and derivatives or combinations thereof; wherein R9, R10, R1 1 , R12, R13, R14, R15 are independently attached a group selecting from CH 3 , CH 2 OH, CHO, COOH, COO-alkyl, COO-aryl, COO-heterocyclic, COO-heteroaryl, CH 2 Oaryl, CH 2 0- heterocyclic, 0H 2 O- heteroaryl, alkyls group, hydroxyl, acetyl group; wherein R4 and R16 form a divalent radical of formula CH20, CH(OR7)0, or COOR7, wherein R7 is hydrogen, alkyl, angeloyl, tigloyl, senecioyl, dibenzoyl, benzoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, aryl, acyl, heterocylic, heteroraryl, and derivatives thereof; wherein at least two of R1 , R2 and R6 are attached a group selected from O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, 0-3,3- Dimethylartyloyl, O-Cinnamoyl, O-Pentenoyl, O-Hexanoyl, O-benzoyl, O-Ethylbutyryl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, , O-ethanoyl, O-propanoyl, O-propenoyl, O- butanoyl, O-butenoyl, O-pentanoyl, O-hexenoyl, O-heptanoyl, O-heptenoyl, O-octanoyl, O-octenoyl, O-nonanoyl, O-nonenoyl, O-decanoyl, O-decenoyl, O-propionyl, 0-2- propenoyl, O-2-butenoyl, O-lsobutyryl, O-2-methylpropanoyl, O-2-ethylbutyryl, O- ethylbutanoyl, O-2-ethylbutanoyl, O-butyryl, O- (E)-2,3-Dimethylacryloyl, 0-(E)-2- Methylcrotonoyl, O-3-c/s-Methyl-methacryloyl, 0-3-Methyl-2-butenoyl, 0-3- Methylcrotonoyl, O-4-Pentenoyl, 0-(2E)-2-pentenoyl, O-Caproyl, O-5-Hexenoyl, O- Capryloyl, O-Lauroyl, O-Dodecanoyl, O-Myristoyl, O-Tetradecanoyl, O-Oleoyl, 0-C(2- 18) Acyl and derivatives thereof; or at least one of R1 , R2, and R4 is a sugar moiety having at least two groups selected from a group consisting of angeloyl, acetyl, tigloyl, senecioyl, Crotonoyl, 3,3-Dimethylartyloyl, Cinnamoyl, Pentenoyl, Hexanoyl, benzoyl, Ethylbutyryl, benzoyl, dibenzoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, aryl, acyl, heterocylic, heteroraryl, ethanoyl, propanoyl, propenoyl, butanoyl, butenoyl, pentanoyl, hexenoyl, heptanoyl, heptenoyl, octanoyl, octenoyl, nonanoyl, nonenoyl, decanoyl, decenoyl, propionyl, 2-propenoyl, 2-butenoyl, Isobutyryl, 2-methylpropanoyl, 2-ethylbutyryl, ethylbutanoyl, 2-ethylbutanoyl, butyryl, (E)-2,3-Dimethylacryloyl, (E)-2- Methylcrotonoyl, 3-c/s-Methyl-methacryloyl, 3-Methyl-2-butenoyl, 3-Methylcrotonoyl, 4- Pentenoyl, (2E)-2-pentenoyl, Caproyl, 5-Hexenoyl, Capryloyl, Lauroyl, Dodecanoyl, Myristoyl, Tetradecanoyl, Oleoyl, 0-C(2-18) Acyl and their derivatives thereof; or wherein R4 represents CH 2 R6, wherein R6 is selected from hydroxyl, O-angeloyl, O- tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, 0-3,3-Dimethylartyloyl, O-Cinnamoyl, O- Pentenoyl, O-Hexanoyl, O-Ethylbutyryl, O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O- alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O- alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O- alkenylcarbonyl and derivatives thereof; wherein R5 is/are the sugar moiety(ies) selected from the following sugars and alduronic acids: glucose, galactose, rhamnose, arabinose, xylose, fucose, allose, altrose, gulose, idose, lyxose, mannose, psicose, ribose, sorbose, tagatose, talose, fructose, glucuronic acid, gaiacturonic acid; or their derivatives thereof, In an embodiment, wherein R5 is a hydroxyl, O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, 0-3,3-Dimethylartyloyl, O-Cinnamoyl, O-Pentenoyl, O-Hexanoyl, O-benzoyl, O-Ethylbutyryl, O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O- alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O- alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O- alkenylcarbonyl and derivatives thereof. In an embodiment, R1 , R2, R3, R4, R5, R8, R9, R10, R1 1 , R12, R13, R14 or R15 comprise of one or more sugar moieties. In an embodiment, R1 , R2, R3, R4, R5, R8, R9, R10, R1 1 , R12, R13, R14 or R15 comprise of one or more acids. In an embodiment, at least 1 , or 2, or 3, or 4 of R1 , R2, R3, R4, R5, R8, R9, R10, R1 1 , R12, R13, R14 and R15 is hydroxyl. In an embodiment, at least 2, or 3, or 4, or 5, or 6, or 7 of R1 , R2, R3, R4, R5, R8, R9, R10, R1 1 , R12, R13, R14 and R15 are independently attached a group selected from the group of O-acetyl, O- angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, 0-3,3-Dimethylartyloyl, O- Cinnamoyl, O-Pentenoyl, O-Hexanoyl, O-benzoyl, O-Ethylbutyryl, O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyI, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyI substituted phenyl, O-aryl, O-acyl, O-heterocylic, O- heteroraryl, O-alkenylcarbonyl, alkane, alkene and derivatives thereof, wherein the group is attached to the triterpene directly or by connecting moiety(ies); In an embodiment, at least 1 or 2, or 3, or 4, or 5, or 6, or 7 of R1 , R2, R3, R4, R5, R8 and R10 are independently attached a group selected from the group of O-angeloyl, O- tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, 0-3,3-Dimethylartyloyl, O-Cinnamoyl, O- Pentenoyl, O-Hexanoyl, O-benzoyl, 0-Ethylbutyryl,0-alkyl, O-dibenzoyl, O-benzoyl, O- alkanoyi, O-alkenoyI, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyI substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O- alkenylcarbonyl, O-ethanoyl, O-propanoyl, O-propenoyl, O-butanoyl, O-butenoyl, O- pentanoyl, O-hexenoyl, O-heptanoyl, O-heptenoyl, O-octanoyl, O-octenoyl, O- nonanoyl, O-nonenoyl, O-decanoyl, O-decenoyl, O-propionyl, O-2-propenoyl, 0-2- butenoyl, O-lsobutyryl, O-2-methylpropanoyl, O-2-ethylbutyryl, O-ethylbutanoyl, 0-2- ethylbutanoyl, O-butyryl, O- (E)-2,3-Dimethylacryloyl, 0-(E)-2-Methylcrotonoyl, O-3-c/s- Methyl-methacryloyl, 0-3-Methyl-2-butenoyl, O-3-Methylcrotonoyl, O-4-Pentenoyl, O- (2E)-2-pentenoyl, O-Caproyl, O-5-Hexenoyl, O-Capryloyl, O-Lauroyl, O-Dodecanoyl, O- Myristoyl, O-Tetradecanoyl, O-Oleoyl, 0-C(2-18) Acyl, CH20-angeloyl, CH20-tigloyl, CH20-senecioyl, CH20-acetyl, CH20-Crotonoyl, CH20-3,3-Dimethylartyloyl, CH20- Cinnamoyl, CH20-Pentenoyl, CH20-Hexanoyl, CH20-benzoyl, CH20-Ethylbutyryl, CH3, CH20H, CH20-alkyl, CH20-dibenzoyl, CH20-benzoyl, CH20-alkanoyl, CH20- alkenoyl, CH20-benzoyl alkyl substituted 0-alkanoyl, CH20-alkanoyl substituted phenyl, CH20-alkenoyl substituted phenyl, CH20-aryl, CH20-acyl, CH20-heterocylic, CH20- heteroraryl, CH20-alkenylcarbonyl, CH20-ethanoyl, CH20-propanoyl, CH20-propenoyl, CH20-butanoyl, CH20-butenoyl, CH20-pentanoyl, CH20-hexenoyl, CH20-heptanoyl, CI-120-heptenoyl, CH20-octanoyl, CH20-octenoyl, CH20-nonanoyl, CH20-nonenoyl, CH20-decanoyl, CH20-decenoyl, CH20-propionyl, CH20-2-propenoyl, CH20-2- butenoyl, CH20-lsobutyryl, CH20-2-methylpropanoyl, CH20-2-ethylbutyryl, CH20- ethylbutanoyl, CH20-2-ethylbutanoyl, CH20-butyryl, CH20-(E)-2,3-Dimethylacryloyl, CH20-(E)-2-Methylcrotonoyl, CH20-3-c/s-Methyl-methacryloyl, CH20-3-Methyl-2- butenoyl, CH20-3-Methylcrotonoyl, CH20-4-Pentenoyl, CH20-(2E)-2-pentenoyl, CH20-Caproyl, CH20-5-Hexenoyl, CH20-Capryloyl, CH20-Lauroyl, CH20- Dodecanoyl, CH20-Myristoyl, CH20-Tetradecanoyl, CH2Q-Oleoyl, CH20-C(2-18) Acyl and derivatives thereof, wherein the group is attached to the triterpene directly or by connecting moiety(ies). In an embodiment, the cancers comprise breast cancer, leukocytic cancer, liver cancer, ovarian cancer, bladder cancer, prostatic cancer, skin cancer, bone cancer, brain cancer, leukemia cancer, lung cancer, colon cancer, CNS cancer, melanoma cancer, renal cancer, cervical cancer, esophageal cancer, testicular cancer, spleenic cancer, kidney cancer, lymphhatic cancer, pancreatic cancer, stomach cancer and thyroid cancer; wherein the cells comprise breast cell, leukocytic cell, liver cell, ovarian cell, bladder cell, prostatic cell, skin cell, bone cell, brain cell, leukemia cell, lung cell, colon cell, CNS cell, melanoma cell, renal cell, cervical cell, esophageal cell, testicular cell, spleenic cell, kidney cell, lymphhatic cell, pancreatic cell, stomach cell and thyroid cell. In an embodiment, the compound is selected from the structure:
R1 , R2, R3, R4, R5, R8, R9, R10, R1 1 , R12, R13, R14, R15 are independently selected from the group of CH3, CH20H, COOH .hydrogen, hydroxyl, methyl, O-angeloyl, O- tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, 0-3,3-Dimethylartyloyl, O-Cinnamoyl, O- Pentenoyl, O-Hexanoyl, O-benzoyl, O-Ethylbutyryl.O-alkyl, O-dibenzoyl, O-benzoyl, O- alkanoyl, O-alkenoyI, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O- alkenylcarbonyl, O-alkane, O-alkene, O-sugar moiety, O-ethanoyl, O-propanoyl, O- propenoyl, O-butanoyl, O-butenoyI, O-pentanoyl, O-hexenoyl, O-heptanoyl, O-heptenoyI, O-octanoyl, O-octenoyl, O-nonanoyl, O-nonenoyl, O-decanoyl, O-decenoyl, O- propionyl, O-2-propenoyl, O-2-butenoyl, O-lsobutyryl, O-2-methylpropanoyl, 0-2- ethylbutyryl, O-ethylbutanoyl, O-2-ethylbutanoyl, O-butyryl, O- (E)-2,3-Dimethylacryloyl, 0-(E)-2-Methylcrotonoyl, O-3-c/s-Methyl-methacryloyl, 0-3-Methyl-2-butenoyl, 0-3- Methylcrotonoyl, O-4-Pentenoyl, 0-(2E)-2-pentenoyl, O-Caproyl, O-5-Hexenoyl, O- Capryloyl, O-Lauroyl, O-Dodecanoyl, O-Myristoyl, O-Tetradecanoyl, O-Oleoyl, 0-C(2- 18) Acyl, CH20-angeloyl, CH20-tigloyl, CH20-senecioyl, CH20-acetyl, CH20- Crotonoyl, CH20-3,3-Dimethylartyloyl, CH20-Cinnamoyl, CH20-Pentenoyl, CH20- Hexanoyl, CH20-benzoyl, CH20-Ethylbutyryl, CH20-alkyl, CH20-dibenzoyl, CH20- benzoyl, CH20-alkanoyl, CH20-alkenoyl, CH20-benzoyl alkyl substituted O-alkanoyl, CH20-alkanoyl substituted phenyl, CH20-alkenoyl substituted phenyl, CH20-aryl, CH20-acyl, CH20-heterocylic, CH20-heteroraryl, CH20-alkenylcarbonyl, CH20-alkane, CH20-alkene and CH20-sugar moiety, CH20-angeloyl, CH20-tigloyl, CH20-senecioyl, CH20-acetyl, CH20-Crotonoyl, CH20-3,3-Dimethylartyloyl, CH20-Cinnamoyl, CH20- Pentenoyl, CH20-Hexanoyl, CH20-benzoyl, CH20-Ethylbutyryl, CH3, CH20H, CH20- alkyl, CH20-dibenzoyl, CH20-benzoyl, CH20-alkanoyl, CH20-alkenoyl, CH20-benzoyl alkyl substituted O-alkanoyl, CH20-alkanoyl substituted phenyl, CH20-alkenoyl substituted phenyl, CH20-aryl, CH20-acyl, CH20-heterocylic, CH20-heteroraryl,
CH20-alkenylcarbonyl, CH20-ethanoyl, CH20-propanoyl, CH20-propenoyl, CH20- butanoyl, CH20-butenoyl, CH20-pentanoyl, CH20-hexenoyl, CH20-heptanoyl, CH20- heptenoyl, CH20-octanoyl, CH20-octenoyl, CH20-nonanoyl, CH20-nonenoyl, CH20- decanoyl, CI-120-decenoyl, CH20-propionyl, CH20-2-propenoyl, CH20-2-butenoyl, CH20-lsobutyryl, CH20-2-methylpropanoyl, CH20-2-ethylbutyryl, CH20-ethylbutanoyl, CH20-2-ethylbutanoyl, CH20-butyryl, CH20-(E)-2,3-Dimethylacryloyl, CH20-(E)-2- Methylcrotonoyl, CH20-3-c s-Methyl-methacryloyl, CH20-3-Methyl-2-butenoyl, CH20- 3-Methylcrotonoyl, CH20-4-Pentenoyl, CH20-(2E)-2-pentenoyl, CH20-Caproyl, CH20- 5-Hexenoyl, CH20-Capryloyl, CH20-Lauroyl, CH20-Dodecanoyl, CH20-Myristoyl, CH20-Tetradecanoyl, CH20-Oleoyl, CH20-C(2-18) Acyl, (CnH2n)0-angeloyl, (CnH2n)0-tigloyl, (CnH2n)0-senecioyl, (CnH2n)0-acetyl, (CnH2n)0-Crotonoyl, (CnH2n)0-3,3-Dimethylartyloyl, (CnH2n)0-Cinnamoyl, (CnH2n)0-Pentenoyl, (CnH2n)0-Hexanoyl, (CnH2n)0-benzoyl, (CnH2n)0-Ethylbutyryl, (CnH2n)0-alkyl, (CnH2n)0-dibenzoyl, (CnH2n)0-benzoyl, (CnH2n)0-alkanoyl, (CnH2n)0-alkenoyl, (CnH2n)0-benzoyl alkyl substituted O-alkanoyI, (CnH2n)0-alkanoyl substituted phenyl, (CnH2n)0-alkenoyl substituted phenyl, (CnH2n)0-aryl, (CnH2n)0-acyl, (CnH2n)0- heterocylic, (CnH2n)0-heteroraryl, (CnH2n)0-alkenylcarbonyl, (CnH2n)0-alkane, (CnH2n)0-alkene and (CnH2n)0-sugar moiety, wherein n is 1 or 2 or 3 or 4 or over 5 or derivatives thereof; or wherein any 1 or 2 or 3 or 4 of R1 , R2, R3, R4, R5, R8 and R10 are independently attached an O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O- Crotonoyl, 0-3,3-Dimethylartyloyl, O-Cinnamoyl, O-Pentenoyl, O-Hexanoyl, O-benzoyI, O-Ethylbutyryl.O-alkyl, O-dibenzoyl, O-benzoyI, O-alkanoyI, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O- aryl, O-acyl, O-heterocylic, O-heteroraryl, O-alkenylcarbonyl, O-ethanoyl, O-propanoyl, O-propenoyl, O-butanoyl, O-butenoyl, O-pentanoyl, O-hexenoyl, O-heptanoyl, O- heptenoyl, O-octanoyl, O-octenoyl, O-nonanoyl, O-nonenoyl, O-decanoyl, O-decenoyl, O-propionyl, O-2-propenoyl, O-2-butenoyl, O-lsobutyryl, O-2-methylpropanoyl, 0-2- ethylbutyryl, O-ethylbutanoyl, O-2-ethylbutanoyl, O-butyryl, 0-(E)-2,3-Dimethylacryloyl, 0-(E)-2-Methylcrotonoyl, 0-3-c/ ' s-Methyl-methacryloyl, 0-3-Methyl-2-butenoyl, 0-3- Methylcrotonoyl, O-4-Pentenoyl, 0-(2E)-2-pentenoyl, O-Caproyl, O-5-Hexenoyl, O- Capryloyl, O-Lauroyl, O-Dodecanoyl, O-Myristoyl, O-Tetradecanoyl, O-Oleoyl, 0-C(2- 18) Acyl, CH20-angeloyl, CH20-tigloyl, CH20-senecioyl, CH20-acetyl, CH20- Crotonoyl, CH20-3,3-Dimethylartyloyl, CH20-Cinnamoyl, CH20-Pentenoyl, CH20- Hexanoyl, CH20-benzoyl, CH20-Ethylbutyryl, CH3, CH20H, CH20-alkyl, CH20- dibenzoyl, CH20-benzoyl, CH20-alkanoyl, CH20-alkenoyl, CH20-benzoyl alkyl substituted O-alkanoyl, CH20-alkanoyl substituted phenyl, CH20-alkenoyl substituted phenyl, CH20-aryl, CH20-acyl, CH20-heterocylic, CH20-heteroraryl, CH20- alkenylcarbonyl, CH20-ethanoyl, CH20-propanoyl, CH20-propenoyl, CH20-butanoyl, CH20-butenoyl, CH20-pentanoyl, CH20-hexenoyl, CH20-heptanoyl, CH20-heptenoyl, CH20-octanoyl, CH20-octenoyl, CH20-nonanoyl, CH20-nonenoyl, CH20-decanoyl, CH20-decenoyl, CH20-propionyl, CH20-2-propenoyl, CH20-2-butenoyl, CH20- Isobutyryl, CH20-2-methylpropanoyl, CH20-2-ethylbutyryl, CH20-ethylbutanoyl, CH20-2-ethylbutanoyl, CH20-butyryl, CH20-(E)-2,3-Dimethylacryloyl, CH20-(E)-2- Methylcrotonoyl, CH20-3-c/s-Methyl-methacryloyl, CH20-3-Methyl-2-butenoyl, CH20- 3-Methylcrotonoyl, CH20-4-Pentenoyl, CH20-(2E)-2-pentenoyl, CH20-Caproyl, CH20- 5-Hexenoyl, CH20-Capryloyl, CH20-Lauroyl, CH20-Dodecanoyl, CH20-Myristoyl, CH20-Tetradecanoyl, CH20-Oleoyl, CH20-C(2-18) Acyl,; or wherein R9, R1 1 , R12, R13, R14, R15 are independently attached a CH3; or wherein R10 is attached an O- angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, 0-3,3-Dimethylartyloyl, O- Cinnamoyl, O-Pentenoyl, O-Hexanoyl, O-benzoyI, O-Ethylbutyryl.O-alkyl, O-dibenzoyl, O-benzoyI, O-alkanoyI, O-alkenoyI, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyI substituted phenyl, O-alkenoyI substituted phenyl, O-aryl, O-acyl, O-heterocylic, O- heteroraryl, O-alkenylcarbonyl, O-ethanoyl, O-propanoyl, O-propenoyl, O-butanoyl, O- butenoyl, O-pentanoyl, O-hexenoyl, O-heptanoyl, O-heptenoyl, O-octanoyl, O-octenoyl, O-nonanoyl, O-nonenoyl, O-decanoyl, O-decenoyl, O-propionyl, O-2-propenoyl, 0-2- butenoyl, O-lsobutyryl, O-2-methylpropanoyl, O-2-ethylbutyryl, O-ethylbutanoyl, 0-2- ethylbutanoyl, O-butyryl, O- (E)-2,3 : Dimethylacryloyl, 0-(E)-2-Methylcrotonoyl, O-3-c/s- Methyl-methacryloyl, 0-3-Methyl-2-butenoyl, O-3-Methylcrotonoyl, O-4-Pentenoyl, O- (2E)-2-pentenoyl, O-Caproyl, O-5-Hexenoyl, O-Capryloyl, O-Lauroyl, O-Dodecanoyl, O- Myristoyl, O-Tetradecanoyl, O-Oleoyl, 0-C(2-18) Acyl, CH20-angeloyl, CH20-tigloyl, CH20-senecioyl, CH20-acetyl, CH20-Crotonoyl, CH20-3,3-Dimethylartyloyl, CH20- Cinnamoyl, CH20-Pentenoyl, CH20-Hexanoyl, CH20-benzoyl, CH20-Ethylbutyryl, CH3, CH20H, CH20-alkyl, CH20-dibenzoyl, CH20-benzoyl, CH20-alkanoyl, CH20- alkenoyi, CH20-benzoyl alkyl substituted O-alkanoyl, CH20-alkanoyl substituted phenyl, CH20-alkenoyl substituted phenyl, CH20-aryl, CH20-acyl, CH20-heterocylic, CH20- heteroraryl, CH20-alkenylcarbonyl, CH20-ethanoyl, CH20-propanoyl, CH20-propenoyl, CH20-butanoyl, CH20-butenoyl, CH20-pentanoyl, CH20-hexenoyl, CH20-heptanoyl, CH20-heptenoyl, CH20-octanoyl, CH20-octenoyl, CH20-nonanoyl, CH20-nonenoyl, CH20-decanoyl, CH20-decenoyl, CH20-propionyl, CH20-2-propenoyl, CH20-2- butenoyl, CH20-lsobutyryl, CH20-2-methylpropanoyl, CH20-2-ethylbutyryl, CH20- ethylbutanoyl, CH20-2-ethylbutanoyl, CH20-butyryl, CH20-(E)-2,3-Dimethylacryloyl, CH20-(E)-2-Methylcrotonoyl, CH20-3-c/ ' s-Methyl-methacryloyl, CH20-3-Methyl-2- butenoyl, CH20-3-Methylcrotonoyl, CH20-4-Pentenoyl, CH20-(2E)-2-pentenoyl, CH20-Caproyl, CH20-5-Hexenoyl, CH20-Capryloyl, CH20-Lauroyl, CH20- Dodecanoyl, CH20-Myristoyl, CH20-Tetradecanoyl, CH20-Oleoyl, CH20-C(2-18) Acyl; or wherein R4 and/or R10 are independently attached an O-angeloyl, O-tigloyl, O- senecioyl, O-acetyl, O-Crotonoyl, 0-3,3-Dimethylartyloyl, O-Cinnamoyl, O-Pentenoyl, O-Hexanoyl, O-benzoyl, O-Ethylbutyryl, O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O- alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O- alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O- alkenylcarbonyl, O-ethanoyl, O-propanoyl, O-propenoyl, O-butanoyl, O-butenoyl, O- pentanoyl, O-hexenoyl, O-heptanoyl, O-heptenoyl, O-octanoyl, O-octenoyl, O- nonanoyl, O-nonenoyl, O-decanoyl, O-decenoyl, O-propionyl, O-2-propenoyl, 0-2- butenoyl, O-lsobutyryl, O-2-methylpropanoyl, O-2-ethylbutyryl, O-ethylbutanoyl, 0-2- ethylbutanoyl, O-butyryl, O- (E)-2,3-Dimethylacryloyl, 0-(E)-2-Methylcrotonoyl, O-3-c/s- Methyl-methacryloyl, 0-3-Methyl-2-butenoyl, O-3-Methylcrotonoyl, O-4-Pentenoyl, O- (2E)-2-pentenoyl, O-Caproyl, O-5-Hexenoyl, O-Capryloyl, O-Lauroyl, O-Dodecanoyl, O- Myristoyl, O-Tetradecanoyl, O-Oleoyl, 0-C(2-18) Acyl, CH20-angeloyl, CH20-tigloyl, CH20-senecioyl, CH20-acetyl, CH20-Crotonoyl, CH20-3,3-Dimethylartyloyl, CH20- Cinnamoyl, CH20-Pentenoyl, CH20-Hexanoyl, CH20-benzoyl, CH20-Ethylbutyryl, CH3, CH20H, CH20-alkyl, CH20-dibenzoyl, CH20-benzoyl, CH20-alkanoyl, CH20- alkenoyl, CH20-benzoyl alkyl substituted O-alkanoyl, CH20-alkanoyl substituted phenyl, CH20-alkenoyl substituted phenyl, CH20-aryl, CH20-acyl, CH20-heterocylic, CH20- heteroraryl, CH20-alkenylcarbonyl, CH20-ethanoyl, CH20-propanoyl, CH20-propenoyl, CH20-butanoyl, CH20-butenoyl, CH20-pentanoyl, CH20-hexenoyl, CH20-heptanoyl, CH20-heptenoyl, CH20-octanoyl, CH20-octenoyl, CH20-nonanoyl, CH20-nonenoyl, CH20-decanoyl, CH20-decenoyl, CH20-propionyl, CH20-2-propenoyl, CH20-2- butenoyl, CH20-lsobutyryl, CH20-2-methylpropanoyl, CH20-2-ethylbutyryl, CH20- ethylbutanoyl, CH20-2-ethylbutanoyl, CH20-butyryl, CH20-(E)-2,3-Dimethylacryloyl, CH20-(E)-2-Methylcrotonoyl, CH20-3-c/s-Methyl-methacryloyl, CH20-3-Methyl-2- butenoyl, CH20-3-Methylcrotonoyl, CH20-4-Pentenoyl, CH20-(2E)-2-pentenoyl, CH20-Caproyl, CH20-5-Hexenoyl, CH20-Capryloyl, CH20-Lauroyl, CH20- Dodecanoyl, CH20-Myristoyl, CH20-Tetradecanoyl, CH20-Oleoyl, CH20-C(2-18) Acyl; wherein R3 is OH or H or absent; wherein R1 , R2, R3, R5, R8 are OH or H or absent; wherein R9, R1 1 , R12, R13, R 4, and R15 are CH3; or wherein R1 , R2, R5, R8 represent OH; R3 represents OH, H or absent; or wherein R4, R10 represent CH20angeloyl; R9, R11 , R12, R13, R14, R15 represent CH3; or wherein R1 , R2, R5, R8 represent OH or O-tigloyl; R3 represents OH, H, or absent; or wherein R4, R10 represent CH20 tigloyl; R9, R1 1 , R12, R13, R14, R15 represent CH3; wherein the group attaching to the core compound selected from acetyl, angeloyl, tigloyl, senecioyi, Crotonoyl, 3,3-Dimethylartyloyl, Cinnamoyl, Pentenoyl, Hexanoyl, benzoyl, Ethylbutyryl, alkyl, dibenzoyl, benzoyl, methylbutanoyl, methylpropanoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, alkanoyl substituted phenyl, alkenoyl substituted phenyl, aryl, acyl, heterocylic, heteroraryl, alkenylcarbonyl, ethanoyl, propanoyl, propenoyl, butanoyl, butenoyl, pentanoyl, hexenoyl, heptanoyl, heptenoyl, octanoyl, octenoyl, nonanoyl, nonenoyl, decanoyl, decenoyl, propionyl, 2-propenoyl, 2-butenoyl, Isobutyryl, 2- methylpropanoyl, 2-ethylbutyryl, ethylbutanoyl, 2-ethylbutanoyl, butyryl, (E)-2,3- Dimethylacryloyl, (E)-2-Methylcrotonoyl, 3-c/s-Methyl-methacryloyl, 3-Methyl-2-butenoyl, 3-Methylcrotonoyl, 4-Pentenoyl, (2E)-2-pentenoyl, Caproyl, 5-Hexenoyl, Capryloyl, Lauroyl, Dodecanoyl, Myristoyl, Tetradecanoyl, Oleoyl, C(2-18) Acyl are interchangeable; wherein the attached group can be the same group or in combination thereof; wherein the connecting group between the core compound and attached group may be O, S ,S(0), S(0)2, C(O), C(0)0, NH, N-alkyl, CH2 or CH20. In an embodiment, R4 is attached an O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, 0-3,3- Dimethylartyloyl, O-Cinnamoyl, O-Pentenoyl, O-Hexanoyl, O-benzoyl, O-Ethylbutyryl, O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O- alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O-alkenylcarbonyl, O-ethanoyl, O-propanoyl, O-propenoyl, O-butanoyl, O-butenoyl, O-pentanoyl, O-hexenoyl, O-heptanoyl, O-heptenoyl, O- octanoyl, O-octenoyl, O-nonanoyl, O-nonenoyl, O-decanoyl, O-decenoyl, O-propionyl, O-2-propenoyl, O-2-butenoyl, O-lsobutyryl, O-2-methylpropanoyl, O-2-ethylbutyryl, O- ethylbutanoyl, O-2-ethylbutanoyl, O-butyryl, O- (E)-2,3-Dimethylacryloyl, 0-(E)-2- ethylcrotonoyl, O-3-c/s-Methyl-methacryloyl, 0-3-Methyl-2-butenoyl, 0-3- Methylcrotonoyl, O-4-Pentenoyl, 0-(2E)-2-pentenoyl, O-Caproyl, O-5-Hexenoyl, O- Capryloyl, O-Lauroyl, O-Dodecanoyl, O-Myristoyl, O-Tetradecanoyl, O-Oleoyl, 0-C(2- 18) Acyl, CH20-angeloyl, CH20-tigloyl, CH20-senecioyl, CH20-acetyl, CH20- Crotonoyl, CH20-3,3-Dimethylartyloyl, CH20-Cinnamoyl, CH20-Pentenoyl, CH20- Hexanoyl, CH20-benzoyl, CH20-Ethylbutyryl, CH3, CH20H, CH20-alkyl, CH20- dibenzoyl, CH20-benzoyl, CH20-alkanoyl, CH20-alkenoyl, CH20-benzoyl alkyl substituted O-alkanoyl, CH20-alkanoyl substituted phenyl, CH20-alkenoyl substituted phenyl, CH20-aryl, CH20-acyl, CH20-heterocylic, CH20-heteroraryl, CH20- alkenylcarbonyl, CH20-ethanoyl, CH20-propanoyl, CH20-propenoyl, CH20-butanoyl, CH20-butenoyl, CH20-pentanoyl, CH20-hexenoyl, CH20-heptanoyl, CH20-heptenoyl, CH20-octanoyl, CH20-octenoyl, CH20-nonanoyl, CH20-nonenoyl, CH20-decanoyl, CH20-decenoyl, CH20-propionyl, CH20-2-propenoyl, CH20-2-butenoyl, CH20- Isobutyryl, CH20-2-methylpropanoyl, CH20-2-ethylbutyryl, CH20-ethylbutanoyl, CH20-2-ethylbutanoyl, CH20-butyryl, CH20-(E)-2,3-Dimethylacryloyl, CH20-(E)-2- Methylcrotonoyl, CH20-3-c/ ' s-Methyl-methacryloyl, CH20-3-Methyl-2-butenoyl, CH20- 3-Methylcrotonoyl, CH20-4-Pentenoyl, CH20-(2E)-2-pentenoyl, CH20-Caproyl, CH20- 5-Hexenoyl, CH20-Capryloyl, CH20-Lauroyl, CH20-Dodecanoyl, CH20-Myristoyl, CH20-Tetradecanoyl, CH20-Oleoyl, CH20-C(2-18) Acyl, In an embodiment, the connecting group between the functional group of angeloyl, tigloyl, senecioyl, acetyl, Crotonoyl, 3,3-Dimethylartyloyl, Cinnamoyl, Pentenoyl, Hexanoyl, benzoyl, Ethylbutyryl, alkyi, dibenzoyi, benzoyl, alkanoyi, alkenoyi, benzoyl alkyl substituted alkanoyi, alkanoyi substituted phenyl, alkenoyi substituted phenyl, aryl, acyl, heterocylic, heteroraryl, and alkenylcarbonyl ethanoyi, propanoyi, propenoyi, butanoyi, butenoyi, pentanoyi, hexenoyi, heptanoyl, heptenoyl, octanoyl, octenoyl, nonanoyl, nonenoyl, decanoyl, decenoyl, propionyl, 2-propenoyl, 2-butenoyl, Isobutyryl, 2-methylpropanoyl, 2-ethylbutyryl, ethylbutanoyl, 2-ethylbutanoyl, butyryl, (E)-2,3-Dimethylacryloyl, (E)-2-Methylcrotonoyl, 3-c/s-Methyl-methacryloyl, 3-Methyl-2-butenoyl, 3-Methylcrotonoyl, 4-Pentenoyl, (2E)-2- pentenoyl, Caproyl, 5-Hexenoyl, Capryloyl, Lauroyl, Dodecanoyl, Myristoyl, Tetradecanoyl, Oleoyl, C(2-18) Acyl can be O, S ,S(0), S(0)2, C(O), C(0)0, NH, N- alkyl, CH2 or CH20. In an embodiment, wherein any 1 or 2 or 3 or 4 or 5 or 6 of R1 , R2, R3, R4, R5, R8, R9, R10, R11 , R12, R13, R14, R15 are independently selected from the group of A-B, wherein A can be O, S ,S(0), S(0)2, C(O), C(0)0, NH, N-alkyl, CH2 or CH20; wherein B is selected from the group of acetyl, angeloyl, tigloyl, senecioyl, Crotonoyl, 3,3-Dimethylartyloyl, Cinnamoyl, Pentenoyl, Hexanoyl, benzoyl, Ethylbutyryl, alkyl, dibenzoyi, benzoyl, methylbutanoyl, methylpropanoyl, alkanoyi, alkenoyi, benzoyl alkyl substituted alkanoyi, alkanoyi substituted phenyl, alkenoyi substituted phenyl, aryl, acyl, heterocylic, heteroraryl, alkenylcarbonyl, ethanoyi, propanoyi, propenoyi, butanoyi, butenoyi, pentanoyi, hexenoyi, heptanoyl, heptenoyl, octanoyl, octenoyl, nonanoyl, nonenoyl, decanoyl, decenoyl, propionyl, 2-propenoyl, 2-butenoyl, Isobutyryl, 2- methylpropanoyl, 2-ethylbutyryl, ethylbutanoyl, 2-ethylbutanoyl, butyryl, (E)-2,3- Dimethylacryloyl, (E)-2-Methylcrotonoyl, 3-c/s-Methyl-methacryloyl, 3-Methyl-2-butenoyl, 3-Methylcrotonoyl, 4-Pentenoyl, (2E)-2-pentenoyl, Caproyl, 5-Hexenoyl, Capryloyl, Lauroyl, Dodecanoyl, Myristoyl, Tetradecanoyl, Oleoyl and C(2-18) Acyl. In an enbodiment, R1 is A-B. In an enbodiment, R2 is A-B. In an enbodiment, R3 is A-B. In an enbodiment, R4 is A-B. In an enbodiment, R5 is A-B. In an enbodiment, R6 is A-B. In an enbodiment, R7 is A-B. In an enbodiment, R8 is A-B. In an enbodiment, R9 is A-B. In an enbodiment, R10 is A-B. In an enbodiment, R1 1 is A-B. In an enbodiment, R12 is A-B. In an enbodiment, R13 is A-B. In an enbodiment, R14 is A-B. In an enbodiment, R15 is A-B. Liposome is artificially prepared vesicles which made up of a lipid bilayer. Certain sizes of liposome can enter tumour sites from blood due to the enhanced permeability and retention effect. While human blood vessels are all surrounded by endothelial cells bound by tight junctions, those tight junctions binding tumour vessels are leakier than those binding other vessels and thus liposomes are able to enter these vessels to enhance the delivery, efficacy, bioavailability and absorption of liposome enclosed drug. This invention provides methods to use liposomes or nanoparticles capsules as a carrier delivering the compound as medicament, wherein the size of liposomes or nanoparticles capsules is less than 200 nm or 100-200nm or 50-100 nm or 5-50nm or less than 50nm, wherein the medicament is included but not limited for treating cancer, inhibiting cancer growth, inhibiting cancer invasion, inhibiting cancer metastasis, modulating cell adhesion, modulating cell attachment, wherein the compound is selected from formula (2A) or formula (K) at the above. Substitution, deletion and/or addition of any group in the above-described compounds by other group(s) will be apparent to one of ordinary skill in the art based on the teachings of this application. In a further embodiment, the substitution, deletion and/or addition of the group(s) in the compound of the invention does not substantially affect the biological function of the compound is included in the invention.
In an embodiment, the compound is selected from the structures:
-Ang-Q
Compound E4A-Ang-N: Compound E4A-Ang-T:
Compound E4A-Sen-N: Compound E4A-Sen-Q:
Page 62 of 120 - Cro-S:
- Acy-V:
Compound E4A- Acy-N: Compound E4A- Acy-Q:
Compound E4A- Acy-S: Compound E4A- Acy-T:
Compound E4A-Pen-Q: Compound E4A-Pen-S:
Compound E4A-Pen-T: Compound E4A-Pen-U:
Compound E4A-Cin-R:
This invention provides compounds by esterification of core compound (C) or (D1 ) with acetyl chloride, angeloyi chloride, tigloyi chloride, senecioyi chloride, CrotonoyI chloride, 0-3,3-Dimethylartyloyl chloride, Cinnamoyl chloride, Pentenoyl chloride, Hexanoyl chloride, benzoyl chloride, Ethylbutyryl chloride, and isolation of the compounds with HPLC, for treating cancer, inhibiting cancer growth, inhibiting cancer invasion, inhibiting cancer metastasis, modulating cell adhesion, modulating cell attachment, wherein the core compound selected from the following:
Esterification of compounds (A), (C), or (D1 ) with acyl chloride including Tigloyl chloride, angeloyl chloride, Acetyl chloride, Crotonoyl chloride, 3,3-Dimethylartyloyl chloride, senecioyl chloride, Cinnamoyl chloride, Pentenoyl chloride, Hexanoyl chloride, benzoyl chloride , Ethylbutyryl chloride, ethanoyl chloride, propanoyl chloride, propenoyl chloride, butanoyl chloride, butenoyl chloride, pentanoyl chloride, hexenoyl chloride, heptanoyl chloride, heptenoyl chloride, octanoyl chloride, octenoyl chloride, nonanoyl chloride, nonenoyl chloride, decanoyl chloride, decenoyl chloride, propionyl chloride, 2-propenoyl chloride, 2-butenoyl chloride, Isobutyryl chloride, 2- methylpropanoyl chloride, 2-ethylbutyryl chloride, ethylbutanoyl chloride, 2-ethylbutanoyl chloride, butyryl chloride, (E)-2,3-Dimethylacryloyl chloride, (E)-2- ethylcrotonoyl chloride, 3-c/s-Methyl-methacryloyl chloride, 3-Methyl-2-butenoyl chloride, 3- Methylcrotonoyl chloride, 4-Pentenoyl chloride, (2E)-2-pentenoyl chloride, Caproyl chloride, 5-Hexenoyl chloride, Capryloyl chloride, Lauroyl chloride, Dodecanoyl chloride, Myristoyl chloride, Tetradecanoyl chloride, Oleoyl chloride, C(2-18) Acyl chloride,
The compounds vary in composition when the time or temperature of the reaction is changed. The peaks, fractions and compounds are selected according to the activities of times studies and the changes of peaks. The compounds having strong to weak activities are selected and isolated. The anti cancer activities are the TT studies of bone (U20S), lung (H460), bladder(HTB-9), ovary (ES2), colon (HCT1 16), pancreas (Capan), ovary(OVCAR3), prostate (DU145), skin (SK-Mel-5), mouth (KB), kidney (A498), breast (MCF-7), liver (HepG2), brain (T98G), luekemia (K562), cervix (HeLa). The active esterification products are purified with HPLC. The reaction product of mixtures and individual compounds are tested with MTT Cytotoxic Assay. Details of method are in Experiment 3 of the present application. A second esterification of compound can be selected from the above experiment results to produce new active compounds. A partial esterification compound is selected from the above experiments to perform a second or repeated with a third esterification with different acyl chloride in order to produce new active compounds with the experiments in the present application, wherein the compound can be selected from K, (H1) or (H2):
R1 , R2, R3, R4, R5, R8, R9, R10, R1 1 , R12, R13, R14, R15, R16, R17, R18 are independently selected from the group of CH3, CH20H, COOH .hydrogen, hydroxyl, methyl, O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, 0-3,3-
Dimethylartyloyl, O-Cinnamoyl, O-Pentenoyl, O-Hexanoyl, O-benzoyl, O-Ethylbutyryl, O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O- alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl,
O-heterocylic, O-heteroraryl, O-alkenylcarbonyl, O-alkane, O-alkene, O-ethanoyl, O- propanoyl, O-propenoyl, O-butanoyl, O-butenoyl, O-pentanoyl, O-hexenoyl, O- heptanoyl, O-heptenoyl, O-octanoyl, O-octenoyl, O-nonanoyl, O-nonenoyl, O-decanoyl, O-decenoyl, O-propionyl, O-2-propenoyl, O-2-butenoyl, O-lsobutyryl, 0-2- methylpropanoyl, O-2-ethylbutyryl, O-ethylbutanoyl, O-2-ethylbutanoyl, O-butyryl, O- (E)-2,3-Dimethylacryloyl, 0-(E)-2-Methylcrotonoyl, O-3-c/s-Methyl-methacryloyl, 0-3- Methyl-2-butenoyl, O-3-Methylcrotonoyl, O-4-Pentenoyl, 0-(2E)-2-pentenoyl, O- Caproyl, O-5-Hexenoyl, O-Capryloyl, O-Lauroyl, O-Dodecanoyl, O-Myristoyl, O- Tetradecanoyl, O-Oleoyl, 0-C(2-18) Acyl; CH20-angeloyl, CH20-tigloyl, CH20- senecioyl, CH20-acetyl, CH20-Crotonoyl, CH20-3,3-Dimethylartyloyl, CH20- Cinnamoyl, CH20-Pentenoyl, CH20-Hexanoyl, CH20-benzoyl, CH20-Ethylbutyryl, CH3, CH20H, CH20-alkyl, CH20-dibenzoyl, CH20-benzoyl, CH20-alkanoyl, CH20- alkenoyl, CH20-benzoyl alkyl substituted O-alkanoyI, CH20-alkanoyl substituted phenyl, CH20-alkenoyl substituted phenyl, CH20-aryl, CH20-acyl, CH20-heterocylic, CH20- heteroraryl, CH20-alkenylcarbonyl, CH20-ethanoyl, CH20-propanoyl, CH20-propenoyl, CH20-butanoyl, CH20-butenoyl, CH20-pentanoyl, CH20-hexenoyl, CH20-heptanoyl, CH20-heptenoyl, CH20-octanoyl, CH20-octenoyl, CH20-nonanoyl, CH20-nonenoyl, CH20-decanoyl, CH20-decenoyl, CH20-propionyl, CH20-2-propenoyl, CH20-2- butenoyl, CH20-lsobutyryl, CH20-2-methylpropanoyl, CH20-2-ethylbutyryl, CH20- ethylbutanoyl, CH20-2-ethylbutanoyl, CH20-butyryl, CH20-(E)-2,3-Dimethylacryloyl, CH20-(E)-2-Methylcrotonoyl, CH20-3-c/ ' s-Methyl-methacryloyl, CH20-3-Methyl-2- butenoyl, CH20-3-Methylcrotonoyl, CH20-4-Pentenoyl, CH20-(2E)-2-pentenoyl, CH20-Caproyl, CH20-5-Hexenoyl, CH20-Capryloyl, CH20-Lauroyl, CH20- Dodecanoyl, CH20-Myristoyl, CH20-Tetradecanoyl, CH20-Oleoyl, CH20-C(2-18) Acyl; or wherein any 1 or 2 or 3 or 4 of R1 , R2, R3, R4, R5, R8, R10, R16, R17, R18 is/are independently attached an O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, O- 3,3-Dimethylartyloyl, O-Cinnamoyl, O-Pentenoyl, O-Hexanoyl, O-benzoyl, O- Ethylbutyryl.O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyI, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyI substituted phenyl, O-alkenoyl substituted phenyl, O- aryl, O-acyl, O-heterocylic, O-heteroraryl, O-alkenylcarbonyl, O-ethanoyl, O-propanoyl, O-propenoyl, O-butanoyl, O-butenoyl, O-pentanoyl, O-hexenoyl, O-heptanoyl, O- heptenoyl, O-octanoyl, O-octenoyl, O-nonanoyl, O-nonenoyl, O-decanoyl, O-decenoyl, O-propionyl, O-2-propenoyl, O-2-butenoyl, O-lsobutyryl, O-2-methylpropanoyl, 0-2- ethylbutyryl, O-ethylbutanoyl, O-2-ethylbutanoyl, O-butyryl, O- (E)-2,3-Dimethylacryloyl, 0-(E)-2-Methylcrotonoyl, 0-3-c/ ' s-Methyl-methacryloyl, 0-3-Methyl-2-butenoyl, 0-3- ethylcrotonoyl, O-4-Pentenoyl, 0-(2E)-2-pentenoyl, O-Caproyl, O-5-Hexenoyl, O- Capryloyl, O-Lauroyl, O-Dodecanoyl, O-Myristoyl, O-Tetradecanoyl, O-Oleoyl, 0-C(2- 18) Acyl, CH20-angeloyl, CH20-tigloyl, CH20-senecioyl, CH20-acetyl, CH20- Crotonoyl, CH20-3,3-Dimethylartyloyl, CH20-Cinnamoyl, CH20-Pentenoyl, CH20- Hexanoyl, CH20-benzoyl, CH20-Ethylbutyryl, CH3, CH20H, CH20-alkyl, CH20- dibenzoyl, CH20-benzoyl, CH20-alkanoyl, CH20-alkenoyl, CH20-benzoyl alkyl substituted O-alkanoyl, CH20-alkanoyl substituted phenyl, CH20-alkenoyl substituted phenyl, CH20-aryl, CH20-acyl, CH20-heterocylic, CH20-heteroraryl, CH20- alkenylcarbonyl, CH20-ethanoyl, CH20-propanoyl, CH20-propenoyl, CH20-butanoyl, CH20-butenoyl, CH20-pentanoyl, CH20-hexenoyl, CH20-heptanoyl, CH20-heptenoyl, CH20-octanoyl, CH20-octenoyl, CH20-nonanoyl, CH20-nonenoyl, CH20-decanoyl, CH20-decenoyl, CH20-propionyl, CH20-2-propenoyl, CH20-2-butenoyl, CH20- Isobutyryl, CH20-2-methylpropanoyl, CH20-2-ethylbutyryl, CH20-ethylbutanoyl, CH20-2-ethylbutanoyl, CH20-butyryl, CH20-(E)-2,3-Dimethylacryloyl, CH20-(E)-2- Methylcrotonoyl, CH20-3-c s-Methyl-methacryloyl, CH20-3-Methyl-2-butenoyl, CH20- 3-Methylcrotonoyl, CH20-4-Pentenoyl, CH20-(2E)-2-pentenoyl, CH20-Caproyl, CH20- 5-Hexenoyl, CH20-Capryloyl, CH20-Lauroyl, CH20-Dodecanoyl, CH20-Myristoyl, CH20-Tetradecanoyl, CH20-Oleoyl, CH20-C(2-18) Acyl; R9, R1 1 , R12, R13, R14, R15 are independently attached a CH3; or wherein R10 is attached an O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, 0-3,3-Dimethylartyloyl, O-Cinnamoyl, O-Pentenoyl, O-Hexanoyl, O-benzoyl, O-Ethylbutyryl.O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O- alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O- alkenoyi substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O- alkenylcarbonyl, O-ethanoyl, O-propanoyl, O-propenoyl, O-butanoyl, O-butenoyl, O- pentanoyl, O-hexenoyl, O-heptanoyl, O-heptenoyl, O-octanoyl, O-octenoyl, O- nonanoyl, O-nonenoyl, O-decanoyl, O-decenoyl, O-propionyl, O-2-propenoyl, 0-2- butenoyl, O-lsobutyryl, O-2-methylpropanoyl, O-2-ethylbutyryl, O-ethylbutanoyl, 0-2- ethylbutanoyl, O-butyryl, O- (E)-2,3-Dimethylacryloyl, 0-(E)-2-Methylcrotonoyl, O-3-c s- Methyl-methacryloyl, 0-3-Methyl-2-butenoyl, O-3-Methylcrotonoyl, O-4-Pentenoyl, O- (2E)-2-pentenoyl, O-Caproyl, O-5-Hexenoyl, O-Capryloyl, O-Lauroyl, O-Dodecanoyl, O- Myristoyl, O-Tetradecanoyl, O-Oleoyl, 0-C(2-18) Acyl, CH20-angeloyl, CH20-tigloyl, CH20-senecioyl, CH20-acetyl, CH20-Crotonoyl, CH20-3,3-Dimethylartyloyl, CH20- Cinnamoyl, CH20-Pentenoyl, CH20-Hexanoyl, CH20-benzoyl, CH20-Ethylbutyryl, CH3, CH20H, 0H2O-alkyl, CH20-dibenzoyl, CH20-benzoyl, CH20-alkanoyl, CH20- alkenoyl, CH20-benzoyl alkyl substituted O-alkanoyl, CH20-alkanoyl substituted phenyl, CH20-alkenoyl substituted phenyl, CH20-aryl, CH20-acyl, CH20-heterocylic, CH20- heteroraryl, CH20-alkenylcarbonyl, CH20-ethanoyl, CH20-propanoyl, CH20-propenoyl, CH20-butanoyl, CH20-butenoyl, CH20-pentanoyl, CH20-hexenoyl, CH20-heptanoyl, CH20-heptenoyl, CH20-octanoyl, CH20-octenoyl, CH20-nonanoyl, CH20-nonenoyl, CH20-decanoyl, CH20-decenoyl, CH20-propionyl, CH20-2-propenoyl, CH20-2- butenoyl, CH20-lsobutyryl, CH20-2-methylpropanoyl, CH20-2-ethylbutyryl, CH20- ethylbutanoyl, CH20-2-ethylbutanoyl, CH20-butyryl, CH20-(E)-2,3-Dimethylacryloyl, CH20-(E)-2-Methylcrotonoyl, CH20-3-c/ ' s-Methyl-methacryloyl, CH20-3-Methyl-2- butenoyl, CH20-3-Methylcrotonoyl, CH20-4-Pentenoyl, CH20-(2E)-2-pentenoyl, CH20-Caproyl, CH20-5-Hexenoyl, CH20-Capryloyl, CH20-Lauroyl, CH20- Dodecanoyl, CH20-Myristoyl, CH20-Tetradecanoyl, CH20-Oleoyl, CH20-C(2-18) Acyl; or wherein R4 and R10 are independently attached an CH20-angeloyl, CH20-tigloyl, CH20-senecioyl, CH20-acetyl, CH20-Crotonoyl, CH20-3,3-Dimethylartyloyl, CH20- Cinnamoyl, CH20-Pentenoyl, CH20-Hexanoyl, CH20-benzoyl, CH20-Ethylbutyryl, CH20H, CH20-alkyl, CH20-dibenzoyl, CH20-benzoyl, CH20-alkanoyl, CH20-alkenoyl, CH20-benzoyl alkyl substituted O-alkanoyl, CH20-alkanoyl substituted phenyl, CH20- alkenoyl substituted phenyl, CH20-aryl, CH20-acyl, CH20-heterocylic, CH20- heteroraryl, CH20-alkenylcarbonyl, CH20-ethanoyl, CH20-propanoyl, CH20-propenoyl, CH20-butanoyl, CH20-butenoyl, CH20-pentanoyl, CH20-hexenoyl, CH20-heptanoyl, CH20-heptenoyl, CH20-octanoyl, CH20-octenoyl, CH20-nonanoyl, CH20-nonenoyl, CH20-decanoyl, CH20-decenoyl, CH20-propionyl, CH20-2-propenoyl, CH20-2- butenoyl, CH20-lsobutyryl, CH20-2-methylpropanoyl, CH20-2-ethylbutyryl, CH20- ethylbutanoyl, CH20-2-ethylbutanoyl, CH20-butyryl, CH20-(E)-2,3-Dimethylacryloyl, CH20-(E)-2-Methylcrotonoyl, CH20-3-c/s-Methyl-methacryloyl, CH20-3-Methyl-2- butenoyl, CH20-3-Methylcrotonoyl, CH20-4-Pentenoyl, CH20-(2E)-2-pentenoyl, CH20-Caproyl, CH20-5-Hexenoyl, CH20-Capryloyl, CH20-Lauroyl, CH20- Dodecanoyl, CH20-Myristoyl, CH20-Tetradecanoyl, CH20-Oleoyl, CH20-C(2-18) Acyl; or wherein R17 and R18 are independently attached an O-angeloyl, O-tigloyl, O- senecioyl, O-acetyl, O-Crotonoyl, 0-3,3-Dimethylartyloyl, O-Cinnamoyl, O-Pentenoyl, O-Hexanoyl, O-benzoyl, O-Ethylbutyryl.O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O- alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O- alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O- alkenylcarbonyl, O-ethanoyl, O-propanoyl, O-propenoyl, O-butanoyl, O-butenoyl, O- pentanoyl, O-hexenoyl, O-heptanoyl, O-heptenoyl, O-octanoyl, O-octenoyl, O- nonanoyl, O-nonenoyl, O-decanoyl, O-decenoyl, O-propionyl, O-2-propenoyl, 0-2- butenoyl, O-lsobutyryl, O-2-methylpropanoyl, O-2-ethylbutyryl, O-ethylbutanoyl, 0-2- ethylbutanoyl, O-butyryl, O- (E)-2,3-Dimethylacryloyl, 0-(E)-2-Methylcrotonoyl, O-3-c/s- Methyl-methacryloyl, 0-3-Methyl-2-butenoyl, O-3- ethylcrotonoyl, O-4-Pentenoyl, O- (2E)-2-pentenoyl, O-Caproyl, O-5-Hexenoyl, O-Capryloyl, O-Lauroyl, O-Dodecanoyl, O- Myristoyl, O-Tetradecanoyl, O-Oleoyl, 0-C(2-18) Acyl; wherein R3 is OH or H or absent; wherein R1 , R2, R3, R5, R8 are OH or H or absent; wherein R9, R11 , R12, R13, R14, and R15 are CH3; or wherein R1 , R2, R5, R8 represent OH; R3 represents OH, H or absent; R4, R10 represent CH20angeloyl; R9, R1 1 , R12, R13, R14, R15 represent CH3; or wherein R1 , R2, R5, R8 represent OH or O-tigloyl; R3 represents OH, H, or absent; R4, R10 represent CH20 tigloyi; R9, R1 1 , R12, R13, R14, R15 represent CH3; wherein the group attaching to the core compound selected from acetyl, angeloyl, tigloyi, senecioyl, Crotonoyl, 0-3,3-Dimethylartyloyl, Cinnamoyl, Pentenoyl, Hexanoyl, benzoyl, Ethylbutyryl, alkyl, dibenzoyl, benzoyl, methylbutanoyl, methylpropanoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, alkanoyl substituted phenyl, alkenoyl substituted phenyl, aryl, acyl, heterocylic, heteroraryl and alkenylcarbonyl are interchangeable or replaceable thereof. They can be the same group or in combination thereof.
A composition comprising an effective amount of compound selected from the above formula or a salt, ester, metabolite or derivative thereof can be used as a medicament for blocking the invasion, migration, metastasis of cancer cells, inhibiting tumor or cancer cell growth and for treating cancer, wherein the cancers comprise breast cancer, leukocytic cancer, liver cancer, ovarian cancer, bladder cancer, prostatic cancer, skin cancer, bone cancer, brain cancer, leukemia cancer, lung cancer, colon cancer, CNS cancer, melanoma cancer, renal cancer, cervical cancer, esophageal cancer, testicular cancer, spleenic cancer, kidney cancer, lymphhatic cancer, pancreatic cancer, stomach cancer and thyroid cancer.
This invention provides a composition comprising the compounds provided in the invention for treating cancers; for inhibiting viruses; for preventing cerebral aging; for improving memory; improving cerebral functions; for curing enuresis, frequent micturition, urinary incontinence; dementia, Alzheimer's disease, autism, brain trauma, Parkinson's disease or other diseases caused by cerebral dysfunctions; for treating arthritis, rheumatism, poor circulation, arteriosclerosis, Raynaud's syndrome, angina pectoris, cardiac disorder, coronary heart disease, headache, dizziness, kidney disorder; cerebrovascular diseasea; inhibiting NF-kappa B activation; for treating brain edema, severe acute respiratory syndrome, respiratory viral diseases, chronic venous insufficiency, hypertension, chronic venous disease, oedema, inflammation, hemonhoids, peripheral edema formation, varicose vein disease, flu, post traumatic edema and postoperative swelling; for inhibiting blood clots, for inhibiting ethanol absorption; for lowering blood sugar; for regulating adrenocorticotropin and corticosterone levels. This invention provides a composition for Anti-MS, anti-aneurysm, anti-asthmatic, anti-oedematous, anti-inflammatory, anti-bradykinic, anti- capillarihemorrhagic, anti-cephalagic, anti-cervicobrachialgic, anti-eclamptic, anti- edemic, anti-encaphalitic, anti-epiglottitic, anti-exudative, anti-flu, anti-fracture, anti- gingivitic, anti-hematomic, anti-herpetic, anti-histaminic, anti-hydrathritic, anti-meningitic, antioxidant, anti-periodontic, anti-phlebitic, anti-pleuritic, anti-raucedo, anti-rhinitic, anti- tonsilitic, anti-ulcer, anti-varicose, anti-vertiginous, cancerostatic, corticosterogenic, diuretic, fungicide, hemolytic, hyaluronidase inhibitor, lymphagogue, natriuretic, pesticide, pituitary stimulant, thymolytic, vasoprotective, inhibiting leishmaniases, modulating adhesion or angiogenesis of cells, anti-parasitic; increase the expression of the genes: ANGPT2, DDIT3, LIF and NFKB1 Z, and manufacturing an adjuvant composition and venotonic treatment.
Alkenyl means unsaturated linear or branched structures and combinations thereof, having formula R2C=CR2, one or more double bonds therein. Examples of alkenyl groups include vinyl, propenyl, isopropenyl, butenyl, s- and t-butenyl, pentenyl, hexenyl, butadienyl, pentadienyl, and hexadienyl. An aryl is a functional group of organic molecule derived from an aromatic compound such as benzene, a 6-14 membered carbocyclic aromatic ring system comprising 1 -3 benzene rings. If two or more aromatic rings are present, then the rings are fused together, so that adjacent rings share a common bond. Examples include phenyl and naphthyl. The aryl group may be substituted with one or more substitutes independently selected from halogen, alkyl or alkoxy. Acyl is a functional group which can be obtained from an organic acid by the removal of the carboxyl. Acyl groups can be written using the general formula -COR, where there is a double bond between the carbon and oxygen. The names of acyl groups typically end in -yl, such as formyl, acetyl, propionyl, butyryl and benzoyl. Benzoyl is one of the acyls, C 6 H 5 COR, obtained from benzoic acid by the removal of the carboxyl. A heterocyclic compound is a compound containing a heterocyclic ring which refers to a non-aromatic ring having 1 -4 heteroatoms, said ring being isolated or fused to a second ring selected from 3- to 7-membered alicyclic ring containing 0-4 heteroatoms , aryl and heteroaryl , wherein heterocyclic compounds include pyrrolidinyl , pipyrazinyl , morpholinyl , trahydrofuranyl , imidazolinyl , thiomorpholinyl, and the like. Heterocyclyl groups are derived from heteroarenes by removal of a hydrogen atom from any ring atom. Alkanoyl is the general name for an organic functional group RCO-, where R represents hydrogen or an alkyl group. Examples of alkanoyls are acetyl , propionoyl , butyryl , isobutyryl, pentanoyl and hexanoyl. Alkenoyl is an alkenylcarbonyl in which the alkenyl is defined above. Examples are pentenoyl (tigloyl) and pentenoyl (angeloyi). Alkyl is a radical containing only carbon and hydrogen atoms arranged in a chain, branched, cyclic or bicyclic structure or their combinations, having 1 -18 carbon atoms. Examples include but are not limited to methyl, ethyl, propyl isopropyl, butyl, s- and t-butyl, pentyl, hexyl, heptyl, octyl, nonyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. Benzoyl alkyl substituted alkanoyi refers to straight or branched alkanoyi substituted with at least one benzoyl and at least one alkyl, wherein the benzoyl is attached to a straight or branched alkyl. An example of a benzoyl alkyl substituted alkanoyi is benzoyl methyl isobutanoyl. A sugar moiety is a segment of molecule comprising one or more sugars or derivatives thereof or alduronic acid thereof.
(Y)Y3, Y and Y3 represent the same compound. YM and (ACH-Y) represent the same compound. Connecting moiety is a substructure or a group of atoms which connect the functional group to a core compound. Example: angeloyi group is connected by a sugar moiety to a triterpene core.
Acetyl = ethanoyl; Propionyl = methylpropanoyl; Crotonoyl = 2-butenoyl; Isobutyryl = 2- methylpropanoyl; 2-Ethylbutyryl =2-Ethylbutanoyl; Butyryl = n-Butyryl = butanoyl = C-4 Acyl ; trans-2-Methyl-2-butenoyl = (E)-2,3-Dimethylacryloyl chloride = (E)-2- Methylcrotonoyl = 3-c/s-Methyl-methacryloyl =Tigloyl; 3,3-Dimethylacryloyl = 3-Methyl-2- butenoyl = 3-Methylcrotonoyl = Senecioyl; Propionyl chloride = methylpropanoyl ; Hexanoyl = Caproyl; Heptanoyl = Enanthic = Oenanthic; Octanoyl = Capryloyl; Dodecanoyl= Lauroyl; Tetradecanoyl= Myristoyl; C(2-18)Acyl is an acyl group having 2 to 18 carbons. ethanoyl is a C-2 Acyl, propanoyl is a C-3 Acyl, propenoyl is a C-3 Acyl, propionyl is a C-3 Acyl, butanoyl is a C-4 Acyl, butenoyl is a C-4 Acyl, crotonoyl is a C-4 Acyl, pentanoyl is a C-5 Acyl, pentenoyl is a C-5 Acyl, angeloyi is C-5 Acyl, tigloyl is C-5 Acyl, senecioyl is C-5 Acyl, hexanoyl is a C-6 Acyl, hexenoyl is a C-6 Acyl, heptanoyl is a C- 7 Acyl, heptenoyl is a C-7 Acyl, octanoyl is a C-8 Acyl, octenoyl is a C-8 Acyl, nonanoyl is a C-9 Acyl, nonenoyl is a C-9 Acyl, decanoyl is a C-10 Acyl, decenoyl is a C-10 Acyl, lauroyl is a C-12 Acyl, dodecanoyl is a C-12 Acyl, myristoyl is a C-14 Acyl, oleoyl is a C- 18 Acyl. The building blocks used in the invention including triterpenes, hydroxylated triterpenes, acetyl, angeloyl, tigloyl, senecioyl, Crotonoyl, 3,3-Dimethylartyloyl, Cinnamoyl, PentenoyI, HexanoyI, benzoyl, Ethylbutyryl, alkyl, dibenzoyi, benzoyl, methylbutanoyi, methylpropanoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, alkanoyl substituted phenyl, alkenoyl substituted phenyl, aryl, acyl, heterocylic, heteroraryl, alkenylcarbonyl, ethanoyl, propanoyl, propenoyl, butanoyl, butenoyl, pentanoyl, hexenoyl, heptanoyl, heptenoyl, octanoyl, octenoyl, nonanoyl, nonenoyl, decanoyl, decenoyl, propionyl, 2-propenoyl, 2-butenoyl, Isobutyryl, 2-methylpropanoyl, 2- ethylbutyryl, ethylbutanoyl, 2-ethylbutanoyl, butyryl, (E)-2,3-Dimethylacryloyl, (E)-2- MethylcrotonoyI, 3-c/s-Methyl-methacryloyl, 3-Methyl-2-butenoyl, 3-Methylcrotonoyl, 4- Pentenoyl, (2E)-2-pentenoyl, Caproyl, 5-Hexenoyl, Capryloyl, Lauroyl, Dodecanoyl, M risto l, Tetradecano l and Oleo l, or halides thereof, or chloride.there
Dimethylartyloyl chloride ° , Cinnamoyl chloride
PentenoyI chloride , benzoyl
4-Pentenoyl chloride CI ( HexanoyI chloride H3C OleoyI chloride
Acryloyl chloride [Synonym: 2-propenoly chloride]; Propionyl chloride [Synonym: methylpropanoyl chloride]; Crotonoyl chloride [Synonym: 2-butenoyl chloride]; Isobutyryl chloride [Synonym: 2-methylpropanoyl chloride]; 2-Ethylbutyryl chloride [Synonym: 2- Ethylbutanoyl chloride]; Butyryl chloride (Synonym: n-Butyryl chloride, butanoyl chloride, or C-4 Acyl halide); f/"ans-2-Methyl-2-butenoyl chloride [Synonym: (E)-2,3- Dimethylacryloyl chloride, (E)-2-Methylcrotonoyl chloride, 3-c/s-Methyl-methacryloyl chloride, Tigloyl chloride]; 3,3-Dimethylacryloyl chloride [Synonym: 3-Methyl-2-butenoyl chloride, 3-Methylcrotonoyl chloride, Senecioyl chloride ]; Hexanoyl chloride [Synonym: Caproyl chloride]; Heptanoyl chloride [Synonym: Enanthic chloride, Oenanthic chloride] Octanoyl chloride [Synonym: Capryloyl chloride ]
In the presented experiments, concentrations of drug that inhibit 15% cell-growth or less (i.e. 85% of control or above) as compared to the no-drug control (DMSO) are considered non-cytotoxic concentrations. In an embodiment, the concentrations of drug that inhibit 10% cell-growth or less (i.e. 90% of control or above) as compared to the no- drug control (DMSO) are considered non-cytotoxic concentrations. In an embodiment, the concentrations of drug that inhibit 5% cell-growth or less (i.e. 95% of control or above) as compared to the no-drug control (DMSO) are considered non-cytotoxic concentrations. In an embodiment, the concentrations of drug that inhibit 20% cell- growth or less (i.e. 80% of control or above) as compared to the no-drug control (DMSO) are considered non-cytotoxic concentrations. In an embodiment, the concentrations of drug that inhibit 25% cell-growth or less (i.e. 75% of control or above) as compared to the no-drug control (DMSO) are considered non-cytotoxic concentrations. In an embodiment, the concentrations of drug that inhibit 30% cell- growth or less as compared to the no-drug control (DMSO) are considered non- cytotoxic concentrations. In an embodiment, the concentrations of drug that inhibit 45% cell-growth or less as compared to the no-drug control (DMSO) are considered non- cytotoxic concentrations.
The triterpene compound or compounds selected from this invention can be administered to a subject in need thereof, treating the subject, wherein including preventing cancer, or providing an adjuvant effect to the subject, or inhibiting the initation or promotion of cancer, or killing the cancer/tumor cells, or inhibiting cancer cell invasion. In an embodiment the compounds inhibit the activation of Nuclear Factor-kB, wherein inhibiting the localization or wherein binding the DNA. In an embodiment the compounds induce apoptosis in cancer cells.
Determination of gene expression by Real-time PCR method (Brilliant QPCR, Agilent Technologies): The real-time polymerase chain reactions further confirm the results obtained from microarray analysis. The Real-time PCR results (shown below) confirmed that Compound Y3 and YM increase the expression of the genes: ANGPT2, DDIT3, LIF and NFKB1Z, wherein the results in Table 19-21 disclosed in PCT/US09/34115, filed February 13, 2009.
The saponins are partially hydrolyzed into a mixture of products which can be separated by HPLC. Specific partial hydrolysis of saponins can also be achieved with enzymes. The glycosidases catalyze the hydrolysis of the glycosidic linkage. Galactosidase is an enzyme which catalyzes the hydrolysis of galactosides. Glucosidase is an enzyme which breaks glucose from saponin. Other enzyme examples are xylanases, lactase, amylase, chitinase, sucrase, maltase, and neuraminidase.
The sugar moiety of the triterpenoid saponin (example Xanifolia Y) can be removed by acid hydrolysis. The synthetic compound of ACH-Y is obtained. ACH-Y is a triterpene with acyl groups but no sugar moiety. The acyl group of the saponin (example Xanifolia Y) can be removed by alkaline hydrolysis. The synthetic compound AKOH-Y can be obtained. AKOH-Y is a pentacyclic triterpene with sugar moieties. A pentacyclic triterpene can be obtained by acid and alkaline hydroysis of saponins from natural sources. A pentacyclic triterpene can be obtained by synthetic methods (Reference: Surendra et al., Rapid and Enantioselective Synthetic Approches to Germanicol and Other Pentacyclic Triterpenes, Journal of the American Chemical Society, 2008, 130(27), 8865-8869). Pentacyclic triterpenes with sugar moieties can also be obtained by synthesis (Reference: Pie et al., Synthesis of L-arabinopyranose containing hederagenin saponins, Tetrahedron 61 (2005) 4347-4362). Acylation is the process of adding an acyl group to a compound. The Friedel-Crafts reaction is an example of this process. An active compound can be obtained by acylating a pentacyclic triterpenes, or hydroxylated triterpenes. In an embodiment, acylating C24, C28, C21 and C22 of a pentacyclic triterpenes, or hydroxylated triterpenes produce compounds for inhibiting cancer growth, cancer invasion, cell invasion, cancer cell invasion, molecular cell invasion, cell attachment adhesion, or cell circulation. In an embodiment, the acyl group(s) may be at C3. In an embodiment, a sugar moiety is at C21 , 22, or 28, wherein the sugar moiety is attached with 2 acyl groups. In an embodiment, acylating the compounds of (A), (B), (C), (D1 ), (D2), (F), (G), (H), produce the compounds for inhibiting cancer invasion, cells invasion or cancer cell invasion; cancer metastasis; or cancer growth The building blocks in the present application are used to synthesise active saponins.
Acylating the compound (G) with angeloyl or tigloyl group gives the following compounds
wherein R1 , R2, R5, R8 represent OH or O-angeloyl; R3 represents OH, H or O- angeloyl; R4, R10 represent CH3, CH20H or CH20angeloyl; R3 represents OH, H or O-angeloyl; R9, R1 1 , R12, R13, R14, R15 represent CH3; or wherein R1 , R2, R5, R8 represent OH or O-tigloyl; R3 represents OH, H or O- tigloyl; R4, R10 represent CH3, CH20H or CH20 tigloyl; R9, R1 1 , R12, R13, R14, R15 represent CH3; wherein the compounds inhibit cancer growth, cancer invasion, cells invasion or cancer cell invasion.
Acylating the compound (G) with angeloyl, tigloyl, senecioyl, acetyl, Crotonoyl, 3,3-
Dimethylartyloyl, Cinnamoyl, Pentenoyl, Hexanoyl, benzoyl, Ethylbutyryl, alkyl, dibenzoyl, benzoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted O-alkanoyl, alkanoyl substituted phenyl, alkenoyl substituted phenyl, aryl, acyl, heterocylic, heteroraryl, CH20-alkenylcarbonyl, alkane, alkene give the compound (K) wherein R1 , R2, R5, R8 represent OH, O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, 0-3,3- Dimethylartyloyl, O-Cinnamoyl, O-Pentenoyl, O-Hexanoyl, O-benzoyl, 0-Ethylbutyryl,0- alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O- alkanoyi, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O-alkenylcarbonyl; R4, R10 represent CH3, CH20H, CH20-angeloyl, CH20-tigloyl, CH20-senecioyl, CH20-acetyl, CH20-Crotonoyl, CH20- 3,3-Dimethylartyloyl, CH20-Cinnamoyl, CH20-Pentenoyl, CH20-Hexanoyl, CH20- benzoyl, CH20-Ethylbutyryl, CH20-alkyl, CH20-dibenzoyl, CH20-benzoyl, CH20- alkanoyi, CH20-alkenoyl, CH20-benzoyl alkyl substituted O-alkanoyl, CH20-alkanoyl substituted phenyl, CH20-alkenoyl substituted phenyl, CH20-aryl, CH20-acyl, CH20- heterocylic, CH20-heteroraryl, CH20-alkenylcarbonyl,alkane, alkene; R3 is absent of represents OH, H, O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, 0-3,3- Dimethylartyloyl, O-Cinnamoyl, O-Pentenoyl, O-Hexanoyl, O-benzoyl, 0-Ethylbutyryl,0- alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O- alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O-alkenylcarbonyl; wherein R9, R11 , R12, R13, R14, R15 represent CH3; wherein the compounds inhibit cancer growth, cancer invasion, cells invasion or cancer cell invasion; wherein the compound for use as mediator or inhibitor of adhesion protein or angiopoietin; wherein the compounds use as mediator modulating the secretion, expression, or synthesis of adhesion protein comprises reducing the fibronectin for inhibiting cell attachment, cell adhesion or cell circulation; wherein the adhesion proteins comprise fibronectin, integrins family, myosin, vitronectin, collagen, laminin, polyglycans, cadherin, heparin, tenascin, · CD 54 , and CAM; the compounds use for anti adhesion therapy and targeting adhesion molecules for therapy.
Applicant further states that anti-adhesion therapy and targeting adhesion molecules for therapy is a new direction for development of drugs. Some examples of anti-adhesion drugs in clinical trials are Efalizumab, Odulimomab, Alicaforsen, Aselizumab etc, which target varies adhesion proteins. Please see TEXT BOOK, Adhesion Molecules: Function and Inhibition, (Reference 2), edited by Klaus Ley page 289-291 , 297.
Adhesion molecules in inflammatory disease, (Reference 4), Abstract, line 7-8 "Blockade of the function of expression of CAM has emerged as a new therapeutic target in inflammatory diseases". Applicants' invention is an anti-adhesion therapy which is a new use of the compound as a mediator or inhibitor of adhesion proteins and angiopoietins. It inhibits excess adhesion and inhibits cell attachment.
In the present application, Applicants have used compounds selected from structure (2A) for anti adhesion therapy, as a mediator or inhibitor of adhesion proteins and angiopoietins, and modulation of the cell attachment, and cell adhesion.
This invention provide a simple semi-synthetic method to obtain semi-natural compounds by chemically removing functional groups of well studied complex natural products to the basic core structure before de-novo chemically adding on active groups directly or sequentially by reaction with the active group donating chemical under different reaction temperature and time to produce series of different active group modified core structure compounds that can be fractionated and easily structurally determined as well as screening for different bio-active efficacies and toxicities as potential new drug candidates.
EXPERIMENTAL DETAILS
Experiment details of herb extraction, analysis of extract components by HPLC, determination of the cell-growth activity effected by Xanifolia Y with cells derived from different human organs using MTT Assay, purification of the bioactive components from plant extract, fractionation of plant extracts with FPLC, isolation of component Ys with preparative HPLC, determination of the chemical structure, cell experiments and animal studying are disclosed in PCT/US05/31900, U.S. Serial No. 11/289142, U.S. Serial 10/906303, U.S. Serial No. 1 1/131551 and U.S. Serial Nos.1 1/683198, filed on March 7, 2007, PCT/US2007/077273, filed August 30, 2007, U.S. Serial No. 60/890380, filed on February 16, 2007, U.S. Nos. 60/947,705, filed on July 3, 2007, PCT/US2008/002086, 1 188-ALA-PCT, filed February 15, 2008, App'l No. PCT/US09/341 15, filed February 13, 2009. Experiments 1 -23 of PCT/US2008/002086, 1 188-ALA-PCT, filed February 15, 2008.
Experiment 1 : Removal of the sugar moiety from saponin by acid hydrolysis
15mg saponin was dissolved in 1 ml of Methanol. 1 ml of 2N HCI was then added. The mixture was refluxed in 80C water bath for 5 hours. The solution was then neutralized by adding 2ml of 1 N NaOH (to final pH 4-6). The aglycone was then extracted with ethylacetate 3ml x 2. The extracts were collected and pooled. Further isolation of aglycone (sugar-removed saponin) was achieved by HPLC with isocratic elution of 80- 100% acetonitrile. Experiment 2: Removal of the acyl group by alkaline hydrolysis
Methods: 20mg of saponin was dissolved in 0.5ml of 1 N NaOH. The solution was incubated in 80C water bath for 4 hours. It was cooled to room temperature before neutralized with 0.5ml 1 N HCI (adjust pH to about 3). The mixture was extracted with 2 ml 1 -butanol 3 times. The butanol fractions were collected and lyophilized. The hydrolyzed saponin with further purified with HPLC in a C-18 column eluted with 25% acetonitrile.
Experiment 3: Adding the acyl group to triterpene by esterification
Method: 40 mg of triterpene core (fraction IV) was dissolved in 1 ml pyridine in a 50 ml tube. Reaction is started by adding 0.2 ml of acyl chloride (Tigloyl chloride, angeloyl chloride, Acetyl chloride, Crotonoyl chloride, 3,3-Dimethylartyloyl chloride( senecioyl chloride), Cinnamoyl chloride, Pentenoyl chloride, Hexanoyl chloride, benzoyl chloride or Ethylbutyryl chloride). The mixture is stirred for 5 sec, 1 min, 2 min, 5 min, 10 min, 30 min, 1 hr, 2 hr, 18 hr, 2 days or 3 days at 0C, 25C or 75C temperature. At the end of reaction, 5 ml of 2N HCI or 1 M NaHC03 is added to the reaction mixture. The solution is then extracted 3 times with 10 ml of ethyl acetate which is then evaporated under vacuum and at 45C and lyophilization. The reaction product is dissolved in 80% acetonitrile - 0.005% Trifluoroacetic acid or DMSO; and was separated with HPLC. Selecting the HPLC fractions for isolation is according to the cytotoxic activity of the reaction product obtained at a specific reaction time. The active esterification products are purified with HPLC. The reaction product of mixtures and individual compounds are tested with MTT cytotoxic assay. Structures are determined with NMR. See examples Figures 1 -12
Experiment 4: Preparation of E4A
1 . Beta-Escin dissolved in 1 M NaOH (20 mg/ml) was incubated at 70C for 5 hours.
2. The hydrolyzed solution was neutralized with HCI and the water was evaporated by lyophilization.
3. The product was dissolved in 50% methanol and 1 N HCI. The mixture was incubated at 70C for 5 hours.
4. The solution was neutralized with NaOH.
5. The hydrolyzed product was extracted with ethylacetate, which was subsequently removed by evaporation.
6. Further purification of the hydrolyzed product (E4A) was archived with FPLC chromatography in a C18 column equilibrated with 70% acetonitrile TFA at the flow rate of 1 ml/min.
Experiment 5: Esterification of E4A with Tigloyl Chloride 1 . 50 mg of E4A in 1 ml pyridine, stir gently in a 50 ml tube. Esterification was carried out at 25C by adding 200 ul Tigloyl chloride.
2. Stir for 1 minute; then immediately add 5 ml of 2N HCI.
3. Stir for 1 hour and sit at room-Temp over night.
4. Extract the esterification products with 10 ml ethylacetate.
5. Evaporate the ethylacetate.
6. Dissolve the sample with 1 ml DMSO.
7. Fractionate the reaction products with HPLC.
8. Collect samples.
Experiment 6: Isolation of E4A-Tig active compounds with HPLC
1 . Column: ZORBAX ODS 9.4x250 mm, 5 urn
2. Solvents: A: 45% AN TFA; B: 100% AN/TFA
3. Chromatography conditions: a) Elution: Solvent A to B in 80 min; then with solvent B for 40 min; b) flow rate: 1 ml/mim. c) Monitor OD: at 207 nm;
Experiment 7: MTT Experiment
Cells. HTB-9 (bladder), Hel_a-S3 (cervix), DU145 (prostate), H460 (lung), MCF-7 (breast), K562 (leukemia), HCT1 16 (colon), HepG2 (liver), U20S (bone), T98G (brain), SK-MEL-5 (Skin) and OVCAR 3, ES2 (ovary), Pancreas(Capan), Mouth(KB), Kidney(A498).
MTT Assay. The procedure for MTT assay followed the method described by Carmichael et al.(1987) with modifications. The cells were seeded into a 96-well plate at for 24 hours before drug-treatment. The cells were then exposed to the drugs for 48, 72, or 96 hours. After the drug-treatment, MTT (0.5 mg/mL) was added to cultures and incubated for an hour. The formazan (product of the reduction of tetrazolium by viable cells) formed and was dissolved with DMSO and the O.D. at 490nm, and was measured by an ELISA reader. The MTT level of the cells before drug-treatment was also measured (TO). The % cell-growth (%G) is calculated as: %G = (TD-T0 / TC-T0) x 100(1 ), where TC or TD represents O.D. readings of control or drug-treated cells.
When TO > TD, then the cytotoxicity (LC) expressed as % of the control is calculated as: %LC = (TD-T0 / TO) x 100(2).
MTT Assay is performed to intermediate and final products from experiments.
Experiment 8: Chemical synthesis, Isolation and characterization of E4A-Tig-R
Chemical synthesis of E4A-Tig-R: 1 . Preparation of E4A; 2. Esterification of E4A with Tigloyl Chloride; 3. Isolation of E4A-Tig-R with HPLC
Cytotoxic activity determination: 1 . MTT assay
Chemical structure determination: 1. NMR analysis; 2. Mass Spectrum analysis Compound E4A-Tig-R: 24,28-0-Tigloyl-3p,16a, 21 β, 22a, 24β, 28-hexahydroxyolean-
12-ene
Experiment 9: Chemical synthesis, Isolation and characterization of E4A-Tig-N
Chemical synthesis of E4A-Tig-N: 1 . Preparation of E4A; 2. Esterification of E4A with Tigloyl Chloride; 3. Isolation of E4A-Tig-N with HPLC
Cytotoxic activity determination: 1. MTT assay
Chemical structure determination: 1. NMR analysis; 2. Mass Spectrum analysis
Experiment 10: Chemical synthesis, Isolation and characterization of E4A-Tig-Q
Chemical synthesis of E4A-Tig-Q: 1. Preparation of E4A; 2. Esterification of E4A with Tigloyl Chloride; 3. Isolation of E4A-Tig-Q with HPLC
Cytotoxic activity determination: 1. MTT assay
Chemical structure determination: 1. NMR analysis; 2. Mass Spectrum analysis
Experiment 11 : Chemical synthesis, Isolation and characterization of E4A-Tig-V Chemical synthesis of E4A-Tig-V: 1. Preparation of E4A; 2. Esterification of E4A with Tigloyl Chloride; 3. Isolation of E4A-Tig-V with HPLC
Cytotoxic activity determination: 1. MTT assay
Chemical structure determination: 1. NMR analysis; 2. Mass Spectrum analysis
Experiment 12: Chemical synthesis, Isolation and characterization of E4A-Tig-T Chemical synthesis of E4A-Tig-T: 1 . Preparation of E4A; 2. Esterification of E4A with Tigloyl Chloride; 3. Isolation of E4A-Tig-T with HPLC
Cytotoxic activity determination: 1. MTT assay
Chemical structure determination: 1 . NMR analysis; 2. Mass Spectrum analysis
Experiment 13: Chemical synthesis, Isolation and characterization of E4A-Tig-U Chemical synthesis of E4A-Tig-U: 1. Preparation of E4A; 2. Esterification of E4A with Tigloyl Chloride; 3. Isolation of E4A-Tig-U with HPLC
Cytotoxic activity determination: 1. MTT assay
Chemical structure determination: 1. NMR analysis; 2. Mass Spectrum analysis
Experiment 14: Chemical synthesis, Isolation and characterization of E4A-Tig-S Chemical synthesis of E4A-Tig-S: 1 . Preparation of E4A; 2. Esterification of E4A with Tigloyl Chloride; 3. Isolation of E4A-Tig-S with HPLC
Cytotoxic activity determination: 1 . MTT assay
Chemical structure determination: 1. NMR analysis; 2. Mass Spectrum analysis
Experiment 15: Using method in Experiment 3, esterification of E4A with acetyl, angeloyl, tigloyl, senecioyl, Crotonoyl, Cinnamoyl, Pentenoyl gave the following compounds:
Compound E4A-Ang-R Compound E4A-Ang-V
-Ang-N:
Compound E4A-Ang-T: Compound E4A-Ang-U:
Compound E4A-Sen-Q: Compound E4A-Sen-S:
Compound E4A-Cro-R: Compound E4A-Cro-V - Cro-T:
Compound E4A- Acy-Q: Compound E4A- Acy-S:
Compound E4A-Pen-R: Compound E4A-Pen-V:
Compound E4A-Pen-Q
Compound E4A-Pen-S: Compound E4A-Pen-T:
-Pen-R:
Compound E4A-Pen-Q: Compound E4A-Pen-S:
Compound E4A-Pen-T: Compound E4A-Cin-U:
Experiment 16: Esterification of E4A-Tig-N with senecioyl chloride
Chemical synthesis of E4A-Tig-Sen-1 : 1. Esterification of E4A-Tig-N with Senecioyl Chloride; 3. Isolation of E4A-Tig-Sen-1 with HPLC
Cytotoxic activity determination: 1. MTT assay
Chemical structure determination: 1. NMR analysis; 2. Mass Spectrum analysis
Experiment 17: Esterification of E4A-Tig-N with angeloyl chloride, Acetyl chloride, Crotonoyl chloride, 3,3-Dimethylartyloyl chloride, senecioyl chloride, Cinnamoyl chloride, Pentenoyl chloride, Hexanoyl chloride, benzoyl chloride or Ethylbutyryl chloride; Isolation with HPLC; Cytotoxic activity determination; Chemical structure determination with the method of Experiment 8, gave the following compounds:
Experiment 18: Inhibition of cell adhesion.
Methods and Results. ES2 or Hey8A cells were plated in T25 flasks with medium containing 5 ug/ml of compounds selected from structure (2A) including E4A-Tig-R, E4A-Tig-V, E4A-Tig-S, E4A-Tig-N, E4A-Tig-Q, E4A-Tig-T. Cultures were incubated for 5 hours. Attached cells were removed from flasks by trypsinization and the numbers/amounts were counted. Compare to no drug controls, 80 ± 4 % of ES2 cells and 60 ± 4 % of Hey8A cells were found attached to flasks under this condition. At 5 ug/ml of above compounds, over 90% of unattached cells are alive as determined by the trypan Blue exclusion assay and by their ability to re-attach to flasks when plating in medium without tested compounds. However, with 10 ug/ml tested compounds, less than 40% of cells attached to flasks and many of them are dead cells. This experiment shows that tested compounds inhibit cells adhesion process.
Experiment 19: Fibronectin secretion experiment
Western blot is applied in this invention as a method to detect the specific proteins in treated and untreated cells with compounds in this invention, wherein the cells are bladder, cervix, prostate, lung, breast, leukemia, colon, liver, bone, brain, Skin, ovary, Pancreas(Capan), Mouth(KB), Kidney.
Cells: targeted cells were grown in RPMI 1640 medium. 1.5 million cells were seeded in a T25 flask and grown for 24 hours before drug-treatment.
Drug-treatment: Cells cultures were replaced with fresh RPMI medium containing either 2.5 ul of DMSO (as control) [D]; or 10, 20, 30, 40, 80 ug/ml of tested compounds. After 24 hours, aliquot of culture medium was taken out for Fibronectin determination (Western blot method).
Cell viability at 24 hours was determined by MTT assay. Cultures were replaced with RPMI medium (5 ml) with MTT and incubated for an hour. The formation of formazan was dissolved in 10 ml of DMSO and OD at 570nm was measured (MTT units).
Western Blot: Spent culture medium was mixed with SDS sample buffer, boiled for 3 minutes before loading to SDS gel. Samples were applied to a 6-10% SDS gel and electrophoresis was conducted with 100 volts for 2 hours. Protein was transferred to a nitrocellulose membrane electrophoretically. The nitrocellulose blot was incubated with the first antibody and second antibody (AP conjugated, Promega S3721 ). The immuno- bands were developed with BCIP/NBT color development system.
Determination of Western blot band intensity: The band-images of Western blot were captured with a digital camera and the intensity of bands was determined using "Image J" software.
Results show that compounds of E4A-Tig-R, E4A-Tig-V, E4A-Tig-S, E4A-Tig-N, E4A- Tig-Q, E4A-Tig-T inhibit fibronectin secretion from 20-40%. in bladder, cervix, prostate, lung, breast, leukemia, colon, liver, bone, brain, Skin, ovary, Pancreas(Capan), Mouth(KB), Kidney.
Experiment 20: Esterification of E4A with Propionyl Chloride
Methods: 50 mg of E4A in 1 ml pyridine, stir gently in a 50 ml tube. Esterification was carried out at 25C by adding 200 ul Propionyl chloride, and immediately withdrawn 200 ul from the mixture and added to 1 ml of 2N HCI. (ASAP sample). At 1 , 2, 5, 10 and 60 minutes afterward; 200 ul of reaction mixture was similarly withdrawn and add to 1 ml of 2N HCI. Mixtures were sit at room-Temp over night. Extract the esterification products with 2 ml ethylacetate. Evaporate the ethylacetate.- Dissolve the sample with DMSO (final concentration of 40 mg/ml). Fractionate the reaction products with HPLC (C18 column, 1 ml/min).
HPLC condition: Column: C18 (9.4 x 250 mm, 5 urn); Solvents: 80% Acetonitrile - 0.005% TFA; Gradient: isocratic; Flow-rate: 1 ml / min; O.D.: 207nm, AT=1024; Chart speed: 0.1 cm/min; Run time: 120 min; MTT assay (Cytotoxicity determination) condition: Cells: ES2 (ovarian cancer). Cell density: platel OK cells per well over night before addition of drug. Drug incubation time: 2 days.
Experiment 21 : Esterification of E4A with Isobutyryl Chloride
Methods: 52 mg of E4A in 1 ml pyridine, stir gently in a 50 ml tube. Esterification was carried out at 25°C by adding 200 ul of isobutyryl chloride. 2 minute later, 4 ml 2N HCI was added to the reaction mixture. Mixtures were kept at room-Temp over night. Extract the esterification products with 5 ml ethyl acetate. Evaporate the ethyl acetate. Dissolve the sample with DMSO (final concentration of 40 mg/ml). Fractionate the reaction products with HPLC (C18 column).
HPLC condition: Column: C18 (9.4 x 250 mm, 5 urn); Solvents: 80% Acetonitrile - 0.005% TFA; Gradient: isocratic; Flow-rate: 1 ml / min; O.D.: 207nm, AT=1024; Chart speed: 0.1 cm/min; Run time: 200 min.
MTT assay (Cytotoxicity determination) condition: Cells: ES2 (ovarian cancer); Cell density: platel OK cells per well over night before addition of drug; Drug incubation time: 2 days.
Experiment 22: Esterification of E4A with 3,3-dimethylacryloly chloride from different times of esterification reaction. Reaction products obtained from each time of reaction (5 sec, 1 min, 2 min, 5 min, and 10 min) were fractionated by HPLC. The profile is plotted according to HPLC elution time and optical density of fractions. Reaction was performed at Room temperature and 0 C. Fractionate the reaction products with HPLC (C18 column). Cytotoxic activity is determined with MTT . Chemical structure determined with NMR.
Experiment 23: Esterification of E4A with Pentenoyl chloride-from different times of esterification reaction. Reaction products obtained from each time of reaction (5 sec, 1 min, 2 min, 5 min, and 10 min) were fractionated by HPLC. The profile is plotted according to HPLC elution time and optical density of fractions. Reaction was performed at Room temperature. Fractionate the reaction products with HPLC (C18 column). Cytotoxic activity is determined with MTT. Chemical structure determined with NMR. Experiment 24: Esterification of E4A with Hexanoly chloride from different times of esterification reaction. Reaction products obtained from each time of reaction (5 sec, 1 min, 2 min, 5 min, and 10 min) were fractionated by HPLC. The profile is plotted according to HPLC elution time and optical density of fractions. Reaction was performed at 0C. Fractionate the reaction products with HPLC (C18 column). Cytotoxic activity is determined with MTT. Chemical structure determined with NMR.
Experiment 25: Esterification of E4A with Acetyl chloride (H) from different times of esterification reaction. Reaction products obtained from each time of reaction (1 min, 2 min, 5 min and 10 min) were fractionated by HPLC. The profile is plotted according to HPLC elution time and optical density of fractions. Reaction was performed at Room temperature. Fractionate the reaction products with HPLC (C18 column). Cytotoxic activity is determined with MTT. Chemical structure determined with NMR. Experiment 26: Esterification products of E4A with Crotonoyl chloride (I) from different times of esterification reaction. Reaction products obtained from each time of reaction (5 sec, 1 min, 2 min, 5 min and 10 min) were fractionated by HPLC. The profile is plotted according to HPLC elution time and optical density of fractions. Reaction was performed at Room temperature. Fractionate the reaction products with HPLC (C18 column). Cytotoxic activity is determined with MTT. Chemical structure determined with NMR.
Experiment 27: Esterification products of E4A with Cinnamoyl chloride (J) from different times of esterification reaction. Reaction products obtained from each time of reaction (1 min, 1 hour, 2 hours, 18 hours, 18 hours(heat) ) were fractionated by HPLC. The profile is plotted according to HPLC elution time and optical density of fractions. Reaction was performed at Room temperature and 75C. Fractionate the reaction products with HPLC (C18 column). Cytotoxic activity is determined with MTT. Chemical structure determined with NMR.
Experiment 28: Esterification products of E4A with pentenoyl, hexanoyl, benzoyl, ethylbutyryl, propionyl, 2-propenoyl, isobutyryl, butyryl, (2E)-2-pentenoyl, 4-Pentenoyl, 5-hexenoyl, heptanoyi, octanoyi, nonanoyi, decanoyi, LauroyI, myristoyi, from different times of esterification reaction. Reaction products obtained from each time of reaction were fractionated by HPLC. The profile is plotted according to HPLC elution time and optical density of fractions. Fractionate the reaction products with HPLC (C18 column). Cytotoxic activity is determined with MTT. Chemical structure determined with NMR.
Experiment 29: Esterification products of E4A with propanoyl, propenoyl, butanoyl, butenoyl, pentanoyl, hexenoyl, heptanoyi, heptenoyl, octanoyi, octenoyl, nonanoyi, nonenoyl, decanoyi, decenoyl, propionyl, 2-propenoyl, 2-butenoyl, Isobutyryl, 2- methylpropanoyl, 2-ethylbutyryl, ethylbutanoyl, 2-ethylbutanoyl, butyryl, (E)-2,3- Dimethylacryloyl, (E)-2-Methylcrotonoyl, 3-c/s-Methyl-methacryloyl, 3-Methyl-2-butenoyl, 3-Methylcrotonoyl, 4-Pentenoyl, (2E)-2-pentenoyl, Caproyl, 5-Hexenoyl, Capryloyl, LauroyI, Dodecanoyl, Myristoyi, Tetradecanoyl, Oleoyl from different times of esterification reaction. Reaction products obtained from each time of reaction were fractionated by HPLC. The profile is plotted according to HPLC elution time and optical density of fractions. Fractionate the reaction products with HPLC (C18 column). Cytotoxic activity is determined with MTT. Chemical structure determined with NMR.