Development of Heterocyclic Hybrids: Efficient Two-Step Synthesis and Antimicrobial Efficacy of Pyridine-4-Thiazolidinone Derivatives

Abstract

We have designed a new series of heterocyclic hybrids incorporating motifs of pyridine and 4-thiazolidinedione for their antimicrobial potential. Synthesizing fourteen derivatives confirmed by spectral data using NMR, IR and MS, of which six (Ch2, Ch4, Ch5, Ch7, Ch10, H2) displayed encouraging antimicrobial potential, especially against Gram-positive/ Gram-negative bacteria and certain fungi, with some showing equal or even better efficacy than standard agents. The obtained MIC values are an indication of potent activity. Mechanistic studies also revealed that the pyridine and 4-thiazolidinedione motifs worked synergistically to disorganize microbial cell membranes and inhibit essential enzymes. More, importantly, the compounds showed their in-vitro therapeutic potential. The above findings suggest that these heterocyclic hybrids may represent a novel series of leads against the growing antimicrobial resistance. Further optimization and studies in-vivo are required to comprehensively evaluate their therapeutic profiles. This research shows the rationale and importance of designing multifunctional molecule with enhanced biological activities.