In vitro α-glucosidase inhibition, molecular dynamics and docking study of phenyl carbamoyl methoxy thiosemicarbazone derivatives as potential anti-diabetic agents

ABSTRRACTAlpha-glucosidase inhibitors have been considered as the most effective agents in preventing hyperglycaemia and alternative targets for the treatment of Diabetes mellitus (DM). This study aimed to synthesise novel phenyl carbamoyl methoxy thiosemicarbazone derivatives and evaluate their potential as α-glucosidase inhibitors through biochemical assays, cytotoxicity screening, molecular docking, and molecular dynamics simulations. The tested derivatives exhibited a range of inhibitory potential, from moderate to strong as compared to acarbose. Derivative 7e revealed the least IC50 value among the tested compounds. 7e in the kinetic assay acted as a competitive inhibitor of the α-glucosidase. The cytotoxic effect 7e was assessed against the A549 and MDA-MB-453 cell lines. MD simulation revealed that <b>7e</b> could affect the stability, flexibility, thermodynamics, and structure of α-glucosidase enzymes such as acarbose. Compound 7e demonstrates strong α-glucosidase inhibitory activity with low cytotoxicity in both cell lines, underscoring its potential as a lead candidate for antidiabetic drug development.