Design, synthesis and biological evaluation of novel oxindole analogs as antitubercular agents.
Yogesh M KhetmalisGuruvelli Pv SangeethaAla Chandunull SwatiSankaranarayanan MurugesanVivek SharmaMuthyala Mk KumarKondapalli Venkata Gowri Chandra SekharPublished in: Future medicinal chemistry (2023)
Aim: To design, synthesize and evaluate oxindole derivatives for antitubercular activity. Methodology: We synthesized the derivatives, confirmed their structures by 1 H/ 13 C 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 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.
Keyphrases
- mycobacterium tuberculosis
- molecular docking
- mass spectrometry
- endothelial cells
- induced apoptosis
- structure activity relationship
- liquid chromatography
- cell proliferation
- pulmonary tuberculosis
- high throughput
- gene expression
- genome wide
- single cell
- oxidative stress
- cell death
- transcription factor
- ms ms
- high performance liquid chromatography
- oxide nanoparticles