期刊
ARCHIVES OF PHARMACAL RESEARCH
卷 40, 期 2, 页码 168-179出版社
PHARMACEUTICAL SOC KOREA
DOI: 10.1007/s12272-016-0882-x
关键词
Antitubercular; p-Aminosalicylic; Dormant TB; Triazole; Isatin; Hydazide and modeling
资金
- Faculty of Pharmacy, Assiut University
The antitubercular drug; para-aminosalicylic acid (PAS) was used as the core scaffold for the design of a series of 1H-1,2,3-triazolylsalicylhydrazones upon coupling with triazole and arylhydrazone moietis to furnish a single molecular architecture. The obtained derivatives were screened against Mycobacterium tuberculosis H37Rv revealing good to high activity for the active compounds (MIC values of 0.39-1.5 mu g/mL) compared to the marketed drugs isoniazid, rifampicin and ethambutol. Moreover, the most active analogue N-(1-(4-chlorobenzyl)-2-oxoindolin-3-ylidene)-2-hydroxy-4-(4-phenyl-1H-1,2,3-triazol-1-yl)-benzohydrazide (20) was found to be ten-fold more potent than PAS and equipotent to rifampicin (MIC 0.39 A mu g/mL), while exhibiting low cytotoxicity with a selectivity index of > 128. In addition, this compound was shown to be active against persistent forms of mycobacteria comparable to standard drugs in nutrient starvation model. Accordingly, we introduce compound 20 as a valuable lead for further development. A 3D-QSAR study was also conducted to help in explaining the observed activity and to serve as a tool for further development.
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