Synthesis and activity of (+)-usnic acid and (-)-usnic acid derivatives containing 1,3-thiazole cycle against Mycobacterium tuberculosis

Synthesis and activity of (+)-usnic acid and (-)-usnic acid derivatives containing 1,3-thiazole cycle against Mycobacterium tuberculosis Full article

Journal

Medicinal Chemistry Research
ISSN: 1054-2523 , E-ISSN: 1554-8120

Output data

Year: 2015, Volume: 24, Number: 7, Pages: 2926-2938 Pages count : 13 DOI: 10.1007/s00044-015-1348-2

Tags

Thiazole; Usnic acid; Tuberculosis; Mycobacterium smegmatis; Mycobacterium tuberculosis; Protein kinase activity; Inhibitory activity

Authors

Bekker Olga B. ¹ , Sokolov Dmitry N. ² , Luzina Olga A. ² , Komarova Nina I. ² , Gatilov Yuriy V. ² , Andreevskaya Sofia N. ³ , Smirnova Tatiana G. ³ , Maslov Dmitry A. ¹ , Chernousova Larisa N. ³ , Salakhutdinov Nariman F. ² , Danilenko Valery.N. ¹

Affiliations

1	(Данные Web of science) Russian Acad Sci, Vavilov Inst Gen Genet, Moscow 119991, Russia
2	(Данные Web of science) Russian Acad Sci, NN Vorozhtzov Novosibirsk Inst Organ Chem, Siberian Branch, Novosibirsk 630090, Russia
3	(Данные Web of science) Russian Acad Med Sci, Cent TB Res Inst, Fed State Budgetary Inst, Moscow 107564, Russia

New usnic acid (UA) derivatives were investigated in vitro to elucidate their potential inhibitory activities on the growth of Mycobacterium smegmatis and Mycobacterium tuberculosis. Seven pairs of enantiomers of thiazole UA derivatives were tested using the M. smegmatis strain mc(2) 155 test system, and the "structure-activity" relationship was established. The most active compounds were (+)-3 and (-)-3, and their kinase inhibitory activities were investigated. The results obtained using the Streptomyces lividans APHVIII+ and M. smegmatis APHVIII+ test systems indicated the significant protein kinase activity of these compounds and revealed the species specificity of the actions of the dextro- and levorotatory isomers. Both isomers, (+)-3 and (-)-3, possess similar inhibitory activity against M. tuberculosis H37Rv. The action of the isomers on eukaryotic cells was also investigated, and the results demonstrate that the dextrorotatory isomer (+)-3 leads to the lysis of intact macrophages to a degree higher than that obtained spontaneously and significantly higher than that obtained with the levorotatory isomer.

Bekker O.B. , Sokolov D.N. , Luzina O.A. , Komarova N.I. , Gatilov Y.V. , Andreevskaya S.N. , Smirnova T.G. , Maslov D.A. , Chernousova L.N. , Salakhutdinov N.F. , Danilenko V.N.
Synthesis and activity of (+)-usnic acid and (-)-usnic acid derivatives containing 1,3-thiazole cycle against Mycobacterium tuberculosis
Medicinal Chemistry Research. 2015. V.24. N7. P.2926-2938. DOI: 10.1007/s00044-015-1348-2 WOS Scopus РИНЦ OpenAlex

Published online:	Mar 1, 2015
Published print:	Jul 1, 2015

Web of science:	WOS:000357468200013
Scopus:	2-s2.0-84943453086
Elibrary:	24959960
OpenAlex:	W1982145061

DB	Citing
Web of science	54
Scopus	53
OpenAlex	60