Synthesis of activity evaluation of flavonoid derivatives as ɑ-glucosidase inhibitors.

Six flavonoid derivatives were synthesized and tested for anti--glucosidase activities. All derivatives were confirmed using NMR and HRMS and exhibited excellent inhibitory effects on -glucosidase. Derivative exhibited the highest anti--glucosidase activity (IC: 15.71 ± 0.21 μM). Structure-activity relationship results showed that bromine group would be the most beneficial group to anti--glucosidase activity. Inhibitory mechnism and inhibition kinetics results showed derivative was a reversible and mixed-type inhibitor. Molecular docking revealed that derivative was tightly bind to the amino acid residues of active pocket of α-glucosidase and formed hydrogen bond, π-π stacking, and Pi-Donor hydrogen with α-glucosidase. Moreover, the physicochemical parameters of all derivatives were assessed using SwissADME software. This results also showed that the hybridization of flavonoid and phenylpropionic acid would be a useful strategy for the development of -glucosidase inhibitors.