Thioflavonols as potent α-glucosidase inhibitors: in vitro, in vivo, and computational analysis

This study investigates the inhibitory potential of a novel series of thioflavonol derivatives (1-12) against α-glucosidase, a key biological macromolecule involved in carbohydrate metabolism, to identify new candidates for type 2 diabetes therapy.

The compounds were evaluated using in vitro enzyme inhibition assays, followed by in vivo antihyperglycemic studies of the most active derivatives. Enzyme kinetics determined the inhibition mechanism, while SAR analysis elucidated structural features governing activity. Computational studies, including molecular docking (PDB IDs: 5NN8 and 8CB1), molecular dynamics simulations, and DFT calculations, explored binding modes and electronic properties. ADMET profiling assessed drug-likeness.

Several derivatives exhibited strong α-glucosidase inhibition, with the most active compound significantly lowering blood glucose levels in vivo. SAR analysis highlighted key substituents contributing to potency. Docking and MD simulations revealed stable enzyme - inhibitor complexes, and DFT supported favorable electronic interactions.

This is the first comprehensive study of thioflavonols as α-glucosidase inhibitors, demonstrating their promising biological activity, stable binding behavior, and favorable pharmacokinetic properties, supporting their potential as novel anti-diabetic agents.