In silico design and synthesis of novel thiazole derivatives as antitubercular agents

Abstract Multi-drug resistant tuberculosis is one of the deadliest diseases growing around the world due to increase in resistance of mycobacteria against the available drugs. Multitarget drug therapy holds considerable importance in addressing various deadly diseases, including tuberculosis. Hence researchers are focused on inhibiting such diseases for human betterment. The targets considered in current research for designing of novel antitubercular agents are mycobacterial MmpL3, InhA, ClpC, LD-transpeptidase, MurX, etc. The purpose of aiming many targets is to inhibit multidrug-resistant tuberculosis completely at its dormant stage as well as in its viable stage. This research highlights the importance of thiazole containing compound with a nitro group as well as a sulfonamide group. Seven novel thiazole derivatives were synthesized and their structures were confirmed by infrared spectroscopy, nuclear magnetic resonance spectroscopy and mass spectroscopy. Compounds were evaluated for their in vitro whole cell activity using Microplate based Alamar Blue Assay against Mycobacterium tuberculosis H37Rv strains results were observed in compounds 3b and 3g exihibited promising activity with minimum inhibitory activity of 12.5 μg/mL. Other synthesized compounds were found to be active against M.tb H37RV strain, but at comparatively higher concentrations (i.e 25μg/mL, 50μg/mL and 100μg/mL).