Title:
USE OF BLUE-LIGHT ACTIVATED BLEBBISTATIN ANALOGUES IN KILLING DRUG-RESISTANT BACTERIA
Document Type and Number:
WIPO Patent Application WO/2021/082512
Kind Code:
A1
Abstract:
Provided herein is the use of biologically inert compounds that can be photoactiveted by blue light at a specific wavelength to remove or kill drug-resistant bacteria. The photoactivatable compounds include blebbistatin analogues such as (R)-blebbistatin. (R)-blebbistatin has no mammalian protein targets and can be photoactivated by blue light to exert significant bactericidal effects. Also provided herein is a method for killing pathogenic bacteria of varied antimicrobial resistance profiles including Staphylococcus aureus, Escherichia coli, Enterococcus spp., Pseudomonas aeruginosa, and Acinetobacter baumannii. Bacterial killing efficiency increases with increasing illumination time, and there is no risk of inducing drug resistance. (R) -blebbistatin is safe to zebrafish embryos after 60 min treatment in vivo. The method is not limited by antibiotic resistance in bacteria, which provides foundation for treating infections by multi-drug resistant pathogens including but not limited to bacteria.
Inventors:
WONG NAI-KEI (CN)
XIE YONG-LI (CN)
YUAN JING (CN)
ZHANG YANG (CN)
ZHOU ZIYUAN (CN)
LI MINGDE (CN)
LIU LEI (CN)
XIE YONG-LI (CN)
YUAN JING (CN)
ZHANG YANG (CN)
ZHOU ZIYUAN (CN)
LI MINGDE (CN)
LIU LEI (CN)
Application Number:
PCT/CN2020/100528
Publication Date:
May 06, 2021
Filing Date:
July 07, 2020
Export Citation:
Assignee:
SHENZHEN THIRD PEOPLES HOSPITAL (CN)
International Classes:
A61K41/00; A01N43/90; A01P1/00; A61L2/00; A61P31/04
Domestic Patent References:
| WO2009001224A2 | 2008-12-31 | |||
| WO2010088803A1 | 2010-08-12 |
Foreign References:
| CN110812481A | 2020-02-21 | |||
| CN110755612A | 2020-02-07 |
Other References:
MIKULICH, A. ET AL.: "Blebbistatin, a myosin inhibitor, is phototoxic to human cancer cells under exposure to blue light.", BIOCHIMICA ET BIOPHYSICA ACTA., vol. 1820, no. 7, 10 April 2012 (2012-04-10), XP028509262, DOI: 10.1016/j.bbagen.2012.04.003
ROMAN BART I., VERHASSELT SIGRID, STEVENS CHRISTIAN V.: "Medicinal Chemistry and Use of Myosin II Inhibitor ( S )-Blebbistatin and Its Derivatives", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 61, no. 21, 8 November 2018 (2018-11-08), US, pages 9410 - 9428, XP055809242, ISSN: 0022-2623, DOI: 10.1021/acs.jmedchem.8b00503
KIRCHNER MARIELUISE, HIGGINS DARREN E.: "Inhibition of ROCK activity allows InlF-mediated invasion and increased virulence of Listeria monocytogenes", MOLECULAR MICROBIOLOGY, WILEY-BLACKWELL PUBLISHING LTD, GB, vol. 68, no. 3, 1 May 2008 (2008-05-01), GB, pages 749 - 767, XP055809240, ISSN: 0950-382X, DOI: 10.1111/j.1365-2958.2008.06188.x
ROMAN BART I., VERHASSELT SIGRID, STEVENS CHRISTIAN V.: "Medicinal Chemistry and Use of Myosin II Inhibitor ( S )-Blebbistatin and Its Derivatives", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 61, no. 21, 8 November 2018 (2018-11-08), US, pages 9410 - 9428, XP055809242, ISSN: 0022-2623, DOI: 10.1021/acs.jmedchem.8b00503
KIRCHNER MARIELUISE, HIGGINS DARREN E.: "Inhibition of ROCK activity allows InlF-mediated invasion and increased virulence of Listeria monocytogenes", MOLECULAR MICROBIOLOGY, WILEY-BLACKWELL PUBLISHING LTD, GB, vol. 68, no. 3, 1 May 2008 (2008-05-01), GB, pages 749 - 767, XP055809240, ISSN: 0950-382X, DOI: 10.1111/j.1365-2958.2008.06188.x
Attorney, Agent or Firm:
GUANGZHOU KEYUE I.P. LAW OFFICE (CN)
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