期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 125, 期 -, 页码 825-841出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2016.09.083
关键词
Tuberculosis; Diaryl urea; Structure-activity relationship; Antimycobacterial activity; Cytotoxicity; Mycolic acid; Cytokines
资金
- Department of Science and Technology (DST), India
- DST, India [SB/FT/CS-008/2013]
- Labex EpiGenMed
Tuberculosis is a major threat for mankind and the emergence of resistance strain of Mycobacterium tuberculosis (Mtb) against first line antibiotics makes it lethal for human civilization. In this study, we have synthesized different diaryl urea derivatives targeting the inhibition of mycolic acid biosynthesis. Among the 39 synthesized molecules, compounds 46, 57, 58 and 86 showed MIC values <= 10 mu g/ml against H37Rv and mc(2)6030 strains. The best molecule with a methyl at ortho position of the first aromatic ring and prenyl group at the meta position of the second aromatic ring showed the MIC value of 5.2 mu g/ml and mu g/ml against H37Rv and mc(2)6030 respectively, with mammalian cytotoxicity of 163.4 mu g/ml. The effective compounds showed selective inhibitory effect on mycolic acid (epoxy mycolate) biosynthesis in C-14-radiolabelled assay. At the same time these molecules also executed their potent immunomodulatory activity by up-regulation of IFN-gamma and IL-12 and down-regulation of IL-10. (C) 2016 Elsevier Masson SAS. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据