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

Abstract

Antimicrobial resistance 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 urgency 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. A three-step multicomponent reaction was performed via imine formation, cyclization, and Knoevenagel condensation for the synthesis of titled compounds (5a-o). The synthesized entities were characterized through different analytical techniques, that is, IR, 1 H NMR, 13 C NMR, and mass spectra. On evaluating the potency of our synthesized hybrids, we received some promising results. Compound 5m was identified as the most potent component possessing 50 μg/ml (minimum inhibitory concentration [MIC] value) against S. aureus and 250 μg/ml (MIC value) against C. albicans strains. Further, a molecular docking study against microbial DNA gyrase was carried out to understand the binding profile of synthesized molecules, which supported their in-vitro antimicrobial activity. These data helped to 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.