Title:
ANTITUBERCULOSIS LANOSTANE TRITERPENOID AND METHOD OF MAKING THE COMPOUNDS
Document Type and Number:
WIPO Patent Application WO/2020/068004
Kind Code:
A3
Abstract:
A new lanostane triterpenoid (24E)-3β-acetoxy-15α-propionyloxylanosta-7,9( 11 ),24-trien-26-oic acid (GA003), is synthesized by acylation reaction of a naturally occurring fungal metabolite, (24E)-3β-acetoxy-15α-hydroxylanosta-7,9( 11 ),24-trien-26-oic acid (ganoderic acid T-O). GA003 is identified as the most potent antimycobacterial against Mycobacterium tuberculosis H37Ra (MIC 0.0977 μg/ml) through a series of structural modifications (semi-synthesis) of a lead natural product, (24E)-3β,15α diacetoxylanosta-7,9(1 1),24-trien-26-oic acid. GA003 exhibits potent growth inhibitory activity against Mycobacterium tuberculosis strains H37Rv (virulent strain), THX-0001 (pre-XDR strain), THX-0002 (XDR strain), and THX-0003 (XDR strain), with MIC values of 0.3125, <0.156, 0.625, and 1.25 μg/ml, respectively, while showing very weak cytotoxicity to Vero cells (African green monkey kidney fibroblasts). Therefore, GA003 and pharmaceutical compositions containing GA003 may be useful for the treatment of tuberculosis.
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Inventors:
ISAKA MASAHIKO (TH)
CHINTHANOM PANIDA (TH)
VICHAI VANICHA (TH)
DOKLADDA KANCHANA (TH)
SAPPAN MALIPAN (TH)
THONGPANCHANG CHAWANEE (TH)
CHINTHANOM PANIDA (TH)
VICHAI VANICHA (TH)
DOKLADDA KANCHANA (TH)
SAPPAN MALIPAN (TH)
THONGPANCHANG CHAWANEE (TH)
Application Number:
PCT/TH2019/000037
Publication Date:
June 25, 2020
Filing Date:
August 30, 2019
Export Citation:
Assignee:
NATIONAL SCIENCE AND TECH DEVELOPMENT AGENCY (TH)
THE THAI LAND RES FUND TRF (TH)
THE THAI LAND RES FUND TRF (TH)
International Classes:
A61P31/06; A61K31/575; C07J9/00
Foreign References:
| US20140294753A1 | 2014-10-02 |
Other References:
ISAKA, P. CHINTANOM, M. SAPPAN, S. SUPOTHINA, V. VICHAI, K. DANWISWTKANJANA, T. BOONPRATUANG, K. D. HYDE, R. CHOEYKLIN: "Antitubercular Activity of Mycelium-Associated Ganoderma Lanostanoids", JOURNAL OF NATURAL PRODUCTS, vol. 80, 15 May 2017 (2017-05-15), pages 1361 - 1369, XP055721228
ARPHA ,C.PHOSRI, N. SUWANNASAI, W. MONGKOLTHANARUK, S. SODNGAM: "Astraodoric Acids A-D: New Lanostane Triterpenes from Edible Mushroom Astraeus odoratus and Their Anti-Mycobacterium tuberculosis H37Ra and Cytotoxic Activity", JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, vol. 60, no. 39, 10 September 2012 (2012-09-10), pages 9834 - 9841, XP055721231
ARPHA ,C.PHOSRI, N. SUWANNASAI, W. MONGKOLTHANARUK, S. SODNGAM: "Astraodoric Acids A-D: New Lanostane Triterpenes from Edible Mushroom Astraeus odoratus and Their Anti-Mycobacterium tuberculosis H37Ra and Cytotoxic Activity", JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, vol. 60, no. 39, 10 September 2012 (2012-09-10), pages 9834 - 9841, XP055721231
Attorney, Agent or Firm:
RUANGSIN, Ratchada et al. (TH)
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