Polyoxometalates: Study of inhibitory kinetics and mechanism against α-glucosidase

Alpha-glucosidase is considered to be an important target for the treatment of noninsulin-dependent diabetes. In this work, the inhibitory effects of polyoxometalates (POMs) affected by three different factors (heteroatom, transition metal substitution element and vanadium substitution number) on alpha-glucosidase were studied. We found that POMs with Keggin-type and vanadium-substituted Dawson-type structures act as effective and mostly competitive inhibitors for alpha-glucosidase (IC50 values around 40-160 mu M) and most compounds can compete with the substrate for the active site of alpha-glucosidase. By analyzing and comparing the inhibitory effects of each series of POMs on alpha-glucosidase, the results demonstrated that the structure and composition of the POMs themselves may indirect influence on their inhibitory capabilities. Moreover, we gained initial information about the structure-inhibition relationship of different POMs. More intriguingly, molecular docking simulation suggested that all compounds bind into the active site of alpha-glucosidase by multiple van-der-Waals and hydrogen bond interactions. Our kinetic data demonstrate the considerable potential of POMs for the development of clinically valuable alpha-glucosidase inhibitors.