Synthesis and biological evaluation of 1,3,4-trisubstituted pyrazole analogues as anti-mycobacterial agents

A series of 1,3,4-trisubstituted pyrazole derivatives (3a–f), (4a–r), (5a–f) and (6a–f) have been synthesized and evaluated for their Mycobacterium tuberculosis (MTB) (H37Rv) inhibitory activity. The structures of newly synthesized compounds were characterized by IR, 1H NMR, 13C NMR and mass spectral analysis. Among the thirty six compounds screened for in vitro anti-mycobacterial activity against MTB, three compounds 3b, 3e and 3f demonstrated significant growth inhibitory activity with minimum inhibitory concentration of 0.78 µg/ml. The selected compounds were further tested for cytotoxic activity against normal human dermal fibroblast cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay and exhibited no significant cytotoxicity. Molecular docking simulation studies were carried out in order to better understand the hypothetical binding interaction to the MTB NADH-dependent enoyl–acyl carrier protein reductase.