Design, Synthesis and Antitubercular Assessment of 1, 2, 3-Triazole Incorporated Thiazolylcarboxylate Derivatives.

A library of 1, 2, 3-triazole incorporated thiazolylcarboxylate derivatives (7a-q) and (8a-j) were synthesized and evaluated for their in-vitro antitubercular activity against Mycobacterium tuberculosis H37Rv. The two compounds 7h and 8h have displayed excellent antitubercular activity with MIC values of 3.12 and 1.56 mu g/mL respectively (MIC values of standard drugs; Ciprofloxacin 1.56 mu g/mL & Ethambutol 3.12 mu g/mL). Whereas, the four com-pounds 7i, 7n, 7p and 8i displayed noticeable antitubercular activity with a MIC value of 6.25 mu g/mL. The active compounds of the series were further studied for their cytotoxicity against RAW264.7 cell line using MTT assay. Furthermore, to study the probable mechanism of antitubercular action, physicochemical property profiling, DFT calculation and molecular docking study were executed on mycobacterial cell wall target Decaprenylphosphoryl-beta-D-ribose 2 '-epimerase 1 (DprE1). Among all the compounds, 7h (-10 kcal/mol) and 8h (-10.1 kcal/mol) exerted the highest negative binding affinity against the targeted DprE1 (PDB: 4NCR) protein.