Synthesis, Biological Evaluation, and Structure–Activity Relationships of Pyrrole Coumarin Conjugates Against Mycobacterium tuberculosis

Considering the escalation of drug-resistant tuberculosis, there is an emerging need to develop new anti-tubercular agents with novel targets. In this context, a series of novel pyrrole coumarin conjugates were synthesized and evaluated against a mycobacterial pathogen panel consisting of Mycobacterium tuberculosis, M. abscessus, M. fortuitum, and M. chelonae. Most of the compounds exhibited selective anti-tubercular activity against M. tuberculosis with MICs ranging from 2 to 64 µg/mL. The active compounds were nontoxic toward Vero cells, demonstrating a favorable selectivity index. The active compounds were also tested against drug-resistant M. tuberculosis (DR-MTB) strains and found to be active against all resistant strains, with MIC values ranging from 2 to 4 µg/mL. Molecular docking studies were performed to gain insight into their mechanism of action, elucidating the potential binding mode and interactions at the enzyme's active site. Further, molecular dynamics simulation studies were carried out to validate the results obtained from the molecular docking study.