Thiazolopyrimidinone schiff bases as dual antimicrobial-antioxidant agents: design, synthesis, biological evaluation, and in‑silico studies

Abstract

A new series of thiazolopyrimidinone Schiff bases (6a-l) were synthesized and characterized for antimicrobial, antioxidant, and computational drug evaluation. The target compounds were obtained via multistep synthesis involving cyclization of 2-amino-3- mercaptopropanoic acid, acylation, hydrazinolysis, and condensation with substituted benzaldehydes. Structures were confirmed by FTIR, ¹H NMR, ¹³C NMR, LC-MS, and elemental analysis.The compounds were screened against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Candida albicans, and Fusarium oxysporum. Derivatives bearing hydroxyl and methoxy substituents (6b, 6f, and 6j) exhibited superior antibacterial and antifungal activity among the synthesized compounds, demonstrating significant inhibitory potential in comparison to other derivatives. In the DPPH radical scavenging assay, these compounds also showed potent antioxidant activity. Molecular docking against DNA gyrase B (PDB ID: 3LD6) and topoisomerase IV (PDB ID: 3SRW) indicated strong binding affinities for 6d, 6i, and 6k, supported by hydrogen bonding and π-π interactions. ADME predictions revealed acceptable pharmacokinetic properties within Lipinski’s parameters. Overall, the synthesized thiazolopyrimidinone Schiff bases demonstrate promising potential as broad-spectrum antimicrobial and antioxidant agents.