Design, Synthesis, and Antimicrobial Evaluation of Novel Pyrimidine–Thiazole Hybrid

Abstract

TPA-1, a 4-aryl pyrimidine derivative linked with a thiazole moiety, was synthesized via a multistep route involving Biginelli condensation, chlorination, and nucleophilic substitution. Structural confirmation was achieved using FTIR, ^1H NMR, ^13C NMR, and mass spectrometry. Molecular docking against DNA Gyrase B revealed moderate binding affinity (−7.8 kcal/mol), supported by hydrogen bonding and hydrophobic interactions. In vitro antimicrobial assays demonstrated moderate inhibition against Staphylococcus aureus, Escherichia coli, and Candida albicans, with MIC values ranging from 64–128 µg/mL. The absence of electron-withdrawing substituents correlated with reduced potency, positioning TPA-1 as a baseline analogue for comparative SAR analysis.