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

© the Partner Organisations 2014. 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.

Publication year:2014