Aim: To design, synthesize and evaluate oxindole derivatives for antitubercular activity. Methodology: We synthesized the derivatives, confirmed their structures by 1H/13C NMR and mass spectrometry, and evaluated them for antitubercular activity against Mycobacterium tuberculosis H37Rv strain using the microplate alamarBlue™ assay. Results: Among all the synthesized derivatives, OXN-1, -3 and -7 exhibited excellent antitubercular activity (minimum inhibitory concentration [MIC]: 0.78 μg/ml). Compounds with a MIC ≤1.56 were tested for cytotoxicity against human embryonic kidney cells and were found to be relatively nontoxic. Molecular docking analysis of OXN-1, -3 and -7 was performed to determine their binding patterns at the active site of DNA topoisomerase II (PDB-5BS8). In drug combination studies, OXN-1, 3 and 7 showed synergism with isoniazid. Conclusion: The obtained results reveal that oxindole derivatives exhibit potent antitubercular activity.
Keywords: hybridization; molecular docking; nitrofuran; oxindole; tuberculosis.