Synthesis, characterisation, and computational investigation of a novel quercetin-derived chromene-4-thione

A novel quercetin-derived chromene-4-thione, 3,5,7-trihydro-2-(3,4-dihydroxyphenyl)-4H-chromene-4-thione (1), was successfully synthesised via a three-step synthetic route involving hydroxyl methylation, sulfurization using Lawson's reagent, and subsequent deprotection. The obtained compound was fully characterised by 1 H NMR, 13 C NMR, and mass spectrometry, confirming the successful structural transformation from the parent flavonoid to the corresponding thione derivative. The synthesised compound exhibited moderate antibacterial activity against Escherichia coli ATCC 8739 and Bacillus cereus ATCC 11778, with inhibition zone diameters of 10.5 ± 0.3 mm and 6.9 ± 0.2 mm, and minimum inhibitory concentrations (MICs) of 75 μM and 150 μM, respectively. In addition, antioxidant activity evaluated by the ABTS assay yielded an IC₅₀ of 6.58 ± 0.16 μM, indicating effective radical scavenging capacity. To gain insight into the structure–property relationship, computational studies including molecular docking, molecular dynamics simulations, ADMET prediction, and density functional theory (DFT) calculations were performed. The results revealed improved binding affinity of compound 1 compared to quercetin toward selected protein targets, along with stable ligand–protein interactions as evidenced by low RMSD values and persistent hydrogen bonding. DFT analysis indicated a reduced HOMO–LUMO energy gap and increased electronic softness, suggesting enhanced chemical reactivity associated with thionation. Overall, this study provides a combined experimental and computational investigation of a quercetin-derived chromene-4-thione, highlighting the impact of structural modification on its physicochemical and biological properties.