N-arylalkylbenzo[d]thiazole-2-carboxamides as anti-mycobacterial agents: design, new methods of synthesis and biological evaluation

Shah, Parth ; Dhameliya, Tejas M. ; Bansal, Rohit ; Nautiyal, Manesh ; Kommi, Damodara N. ; Jadhavar, Pradeep S. ; Sridevi, Jonnalagadda Padma ; Yogeeswari, Perumal ; Sriram, Dharmarajan ; Chakraborti, Asit K. (2014) N-arylalkylbenzo[d]thiazole-2-carboxamides as anti-mycobacterial agents: design, new methods of synthesis and biological evaluation MedChemComm, 5 (10). pp. 1489-1495. ISSN 2040-2503

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Official URL: http://pubs.rsc.org/en/Content/ArticleLanding/2014...

Related URL: http://dx.doi.org/10.1039/C4MD00224E

Abstract

Benzothiazole-2-carboxyarylalkylamides are reported as a new class of potent anti-mycobacterial agents. Forty-one target compounds have been synthesized following a green synthetic strategy using water as the reaction medium to construct the benzothiazole scaffold followed by (i) microwave-assisted catalyst-free and (ii) ammonium chloride-catalyzed solvent-free amide coupling. The anti-mycobacterial potency of the compounds was determined against H37Rv strain. Twelve compounds exhibited promising anti-TB activity in the range of 0.78–6.25 μg mL-1 and were found to be non-toxic (<50% inhibition at 50 μg mL-1) to HEK 293T cell lines with therapeutic index (TI) of 8–64. The most promising anti-TB compound 5bf showed MIC of 0.78 μg mL-1 (TI > 64). The molecular docking studies of 5bf predict it to be a ligand for the M. tuberculosis HisG, the putative drug target for tuberculosis and could serve as a guiding principle for lead optimization.

Item Type:Article
Source:Copyright of this article belongs to Royal Society of Chemistry.
ID Code:100252
Deposited On:20 Jan 2017 09:33
Last Modified:27 Jan 2023 11:48

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