ABSTRACT
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.
ABSTRACT
Among all nitrogen-containing heterocycles, the 1,8-naphthyridine scaffold has recently gained an immense amount of curiosity from numerous researchers across fields of medicinal chemistry and drug discovery. This new attention can be ascribed to its versatility of synthesis, its reactiveness and the variety of biological activities it has exhibited. Over the past half-decade, numerous diverse biological evaluations have been conducted on 1,8-naphthyridine and its derivatives in a quest to unravel novel pharmacological facets to this scaffold. Its potency to treat neurodegenerative and immunomodulatory disorders, along with its anti-HIV, antidepressant and antioxidant properties, has enticed researchers to look beyond its broad-spectrum activities, providing further scope for exploration. This review is a consolidated update of previous works on 1,8-naphthyridines and their analogs, focusing on the past 5 years.
