Molecular docking of polyoxometalates as potential α-glucosidase inhibitors

Abstract α-Glucosidase is an important target enzyme for the treatment of type 2 diabetes in humans. In our previous studies, it was found that polyoxometalates exhibited an effective inhibitory effect on the activity of α-glucosidase, while polyoxometalates have the characteristics of structural diversity and unique properties. Herein, we investigated the inhibition of two different series of polyoxometalates on α-glucosidases by enzyme kinetics and molecular docking. The results demonstrated that all of the studied compounds had a significant inhibitory ability on α-glucosidase as compared with the positive control acarbose. H8[P2Mo17Cr(OH2)O61] reversibly inhibited α-glucosidase in a competitive manner with IC50 of 115.50 ± 1.64 μM and KI value of 44.31 μM. All other compounds reversibly inhibited enzymatic activity in a mixed manner. H6PMo9V3O40 and H8[P2Mo17Cu(OH2)O61] were the best inhibitors in the Keggin and Dawson series, respectively, with IC50 of 9.63 ± 0.43 and 40.13 ± 0.61 μM, respectively. We conducted molecular docking study and found that the compound and α-glucosidase were mainly non-covalently interacting with hydrogen bonds and van der Waals forces. This result further confirmed the inhibition mechanism of enzyme kinetic experiments.