Choline hydroxide mediated eco-friendly synthesis of 5-arylidene thiazol-4(5H)-one clubbed coumarin: antimicrobial evaluation and in silico studies

An efficient and eco-friendly method was developed for synthesizing coumarin–thiazolidinone hybrids using choline hydroxide as a green catalyst. A series of arylidene derivatives (3a–i, 5) were prepared and characterized. Antimicrobial screening against Gram-positive and Gram-negative bacteria, yeast, and fungi demonstrated significant activity, particularly for compound 3c, which produced inhibition zones of up to 30.8 mm against Staphylococcus aureus, and compound 3i, which showed a MIC of 6.25 µg/mL against Escherichia coli, comparable to standard antibiotics. Structure–activity relationship analysis revealed that electron-donating substituents (–OCH₃, indolyl) markedly enhanced potency, while halogen and nitro substituents reduced activity. DFT calculations supported these findings, with 3i showing a low HOMO–LUMO gap (3.183 eV) indicating high reactivity. Molecular docking against Staphylococcus aureus dihydrofolate reductase (PDB: 2XCT) confirmed strong binding, with compound 3c achieving a docking score of –8.6 kcal/mol. These results establish coumarin–thiazolidinone hybrids as promising scaffolds for antimicrobial drug development.