Antitubercular activity of 2-mercaptobenzothiazole derivatives targeting Mycobacterium tuberculosis type II NADH dehydrogenase.

Mycobacterium tuberculosis ( Mtb ) type II NADH dehydrogenase (NDH-2) transports electrons into the mycobacterial respiratory pathway at the cost of reduction of NADH to NAD + and is an attractive drug target. Herein, we have synthesised a series of 2-mercaptobenzothiazoles (C1-C14) and evaluated their anti-tubercular potential as Mtb NDH-2 inhibitors. The synthesised compounds C1-C14 were evaluated for MIC 90 and ATP depletion against Mtb H37Ra, M. bovis , and Mtb H37Rv mc 2 6230. Compounds C3, C4, and C11 were found to be the active molecules in the series and were further evaluated for their MIC 90 against Mtb -resistant strains and for their bactericidal potential against Mtb H37Rv mc 2 6230. The Peredox-mCherry-expressing Mtb strain was used to examine whether C3, C4, and C11 possess NDH-2 inhibitory potential. Furthermore, cytotoxicity analysis against HepG2 displayed a safety index (SI) of >10 for C3 and C4. To get an insight into the mode of interaction at NDH-2, we have performed computational analysis of our active compounds.