Design, synthesis, antimicrobial evaluation, and in-silico studies of some 4-thiazolidinone hybrids bearing coumarin and pyridine moiety

Abstract

Antimicrobial resistance (AMR) is a major threat to mankind. Many frontline medications are ineffective against antimicrobial-resistant strains which are also responsible for the high mortality rate worldwide. The emergence to create new sets of antimicrobial agents is a priority in present circumstances. In continuation to this, we have strategically designed and synthesized some novel hybrids of 4-thiazolidinone bearing coumarin and pyridine cores for the evaluation of antimicrobial efficacy against microbial pathogens. A three-step multicomponent reaction was performed via imine formation, cyclization, and Michael condensation for the synthesis of titled compounds (5a-o). The synthesized compounds were characterized by various analytical techniques i.e., IR, 1H NMR, 13C NMR, and mass spectra. On evaluating the potency of our synthesized hybrids, we received some promising results. Compound 5m was found to be the most active with a MIC value of 50 µg/mL against S. aureus and 250 µg/mL against C. albicans strains. Further, a molecular docking study against microbial DNA gyrase was carried out to understand the binding profile of synthesized molecules, support their in-vitro antimicrobial activity and gain an insight into their plausible mechanism of action. Their binding affinity scores correlated well with the in-vitro antimicrobial activities while their binding modes proposed the involvement of steric, electrostatic, and hydrogen bonding interactions with the active site.