Synergistic exploration of thiazole derivatives: Synthesis, antimicrobial activity and computational insights

Abstract

The emergence of Antimicrobial resistance (AMR) is a transnational concern for maintaining global health in this era, and hence it is essential to find and create newer antimicrobial drugs with unique modes of action and better efficiency. In pursuit of searching new antimicrobial agents, a novel series of thiazole derivatives bearing biologically significant functionalities was efficiently synthesized and evaluated for potential in vitro antimicrobial activities against four bacterial strains viz. two Gram positive strains: S. aureus, S. pyogenes, two Gram negative strains: E. coli, P. aeruginosa and two fungal strains namely, C. albicans, A. niger, in comparison to standard drugs like Ampicillin and Nystatin, respectively. Further, DFT study was performed and these compounds were screened for their binding efficacies against the respective target proteins, followed by prediction of drug-likeness and ADME properties. Among the thiazole derivatives, compounds 6 and 7d were the most active. Interestingly, 7d emerged as a promising candidate, demonstrating greater effectiveness against E. coli and A. niger with an MIC of 18 µg/mL and 50 µg/mL compared to reference drug Ampicillin (MIC = 100 µg/mL) and Nystatin (MIC = 100 µg/mL), respectively. Compound 6 showed excellent activity against E. coli and C. albicans with an MIC of 10 µg/mL and 50 µg/mL compared to Ampicillin (MIC = 100 µg/mL) and Nystatin (MIC = 100 µg/mL), respectively. Molecular dynamic simulation studies were conducted with the target protein for 7d showing excellent biological activity and binding affinity in in silico studies. These results suggest that thiazole derivative 6 and 7d is a promising therapeutic candidate for drug-resistant bacterial and fungal infections.