Exploring Thiazole-Based Heterocycles: Synthesis, Bioactivity, and Molecular Docking for Antimicrobial Applications

Abstract

In response to the rising threat of antimicrobial resistance, a novel series of thiazole-based heterocyclic compounds incorporating benzimidazole, benzoxazole, and benzothiazole via the reaction of 2-chloro-N-(4-(6-methyl-2,4-dioxo-3,4-dihydro-2H-pyran-3-yl)thiazol-2-yl) acetamide (3) with some mercapto derivatives. Pyrazolo[1,5-a]pyrimidine motifs were synthesized via the reaction of aminopyrazole derivative 9 with some electrophilic reagents and systematically characterized. The antimicrobial potential of these molecules was assessed against Staphylococcus aureus, Escherichia coli, and Candida albicans. Among the tested derivatives, compounds 6, 20, and 22 emerged as particularly effective, with minimum inhibitory concentrations (MICs) reaching as low as 3.125 μg/mL. Structure–activity relationship (SAR) analysis highlighted the role of electron-withdrawing groups in enhancing bioactivity. Molecular docking studies further supported the experimental findings, showing favorable interactions with bacterial DNA gyrase (PDB ID: 1KZN). Additionally, SwissADME profiling revealed that the compounds possess promising drug-like properties and oral bioavailability. These findings position the synthesized thiazole-containing scaffolds as promising candidates for future antimicrobial drug development.