Synthesis of coumarin-thioether conjugates as potential anti-tubercular agents: Their molecular docking and X-ray crystal studies

In this work, we report a series of 4-(2,6-dimethylphenyl)thio)methyl)-2H-chromen-2-one conjugates as promising leads to treat tuberculosis. Spectroscopic and other analytical methods were used to validate the synthesised compounds. The compounds were assessed for in vitro anti-tubercular activity with the H 37 Rv strain of Mycobacterium tuberculosis. Further, cytotoxicity studies were performed using Vero cells. Most of the synthesised conjugates were effective and displayed notable activity with MIC values in the range 0.39-12.5 mu g/mL.The most diligent compound 6b (MIC = 0.39 mu g/mL) was twofold more active than standard anti-TB drug Rifampin (0.8 mu g/mL) and was comparable to Isoniazid (0.1 mu g/mL). Compound 6f also displayed exemplary activity (MIC 0.78 mu g/mL). Both compounds 6b and 6f possessed low levels of cytotoxicity, Molecular docking evaluation of the synthesised conjugates and 4DQU ligand demonstrated that the synthesised conjugates had higher C-score values that further supports the obtained results. It indicates compound 6b and 6f are promising lead compounds in search of novel antitubercular drug-like molecules.

Automated summary

This study reported a series of promising lead compounds for the treatment of tuberculosis, which were validated for their anti-tubercular activity and cytotoxicity in vitro. Compounds 6b and 6f showed high activity and low cytotoxicity, making them potential candidates for novel anti-tubercular drug molecules.