Isoquinoline Containing Azo Schiff Derivatives as Potential Antitubercular Agents: Synthesis, Characterization, Molecular Docking, PASS Prediction and ADME Studies

Abstract

A series of isoquinoline containing novel azo Schiff base derivatives (3a-l) were synthesized and characterized by FT-IR, NMR (1H NMR & 13C NMR) and mass spectral analysis. The synthesized title compounds were evaluated for in vitro antitubercular activity against Mycobacterium tuberculosis (MTB) H37Rv strain by microplate alamar blue assay (MABA) method. Among the synthesized series of compounds, the compounds 3a, 3b, 3c and 3d were emerged as excellent antitubercular agents. Compound 3b showed the lowest MIC value of 1.6 μg/mL with a potency equivalent to the standards, isoniazid and ethambutol. Compounds 3a & 3c showed MIC value of 3.125 μg/mL, which is equivalent to the activity of a reference standard pyrazinamide. Compound 3d showed significant activity with MIC of 6.25 μg/mL and other compounds showed good to moderate activity ranging from 12.5 to 50 μg/mL. The four potent components were further tested for in vitro cytotoxicity using MTT assay against MCF-7 and HeLa cell lines to check the selectivity index. Among the tested series, compound 3b possessed the highest cytotoxicity against both MCF-7 (IC50, 7.09 ± 0.41) and HeLa (IC50, 9.04 ± 0.34) cell lines. Additionally, in silico molecular docking was performed to study its binding interaction with Mycobacterium tuberculosis enoyl reductase (InhA) and drug-like features were studied using Swiss ADME tool. PASS analysis of all the compounds showed greater Pa than Pi value for the antituberculosis activity. The results suggested that the synthesized isoquinoline containing azo Schiff base derivatives becomes promising for developing new drugs to treat tuberculosis.