Synthesis, antimicrobial evaluation, and computational investigation of novel thiazole-carbamate hybrids as dual antibacterial and antifungal agents
TL;DR
A new series of thiazole-based carbamate hybrids was synthesized to develop improved antibacterial and antifungal agents and several derivatives emerged as promising antimicrobial candidates through combined biological and computational evaluation.
Abstract
A new series of thiazole-based carbamate hybrids was synthesized to develop improved antibacterial and antifungal agents. The compounds were prepared by reacting aminothiazole with various chloroformates, followed by hydrolysis to obtain carbamate acids, which were then coupled with functionalized amines. Each derivative was characterized using spectroscopic techniques. The antibacterial properties of the synthesized hybrids (5a-5g, 6a-6g, and 7a-7g) were evaluated against S. aureus , S. pyogenes , P. aeruginosa , E. coli , C. albicans , and A. niger. by means of the broth dilution technique. Compounds 5d, 6d, 7d, 5e, and 7g showed high antibacterial activities with an MIC of 62.5 μg/mL against P. aeruginosa and E. coli . Compounds 5a, 5g, 6a, 6f, 6g, and 7d exhibited antifungal activity comparable to the standard drug griseofulvin, with MIC values of 250 μg/mL against C. albicans. Computational studies supported the experimental results. Docking analysis against DNA gyrase identified compounds 5a, 5g, and 6f as promising inhibitors, with docking scores between −6.6 and −7.6 kcal/mol. The stable protein-ligand interactions were determined through molecular dynamics simulations over 100 ns. Overall, several derivatives emerged as promising antimicrobial candidates through combined biological and computational evaluation.