Polyoxomolybdates as α-glucosidase inhibitors: Kinetic and molecular modeling studies.

Noninsulin dependent diabetes mellitus is a serious global disease that is treated by inhibiting α-glucosidase to reduce the glucose content in the blood. Several incompletely satisfactory therapeutic drugs are already on the market. In this report, we showed that polyoxomolybdates based on Keggin-type architecture are promising candidates. Kinetic studies indicate that HPMoO, NaPMoVO, NaPMoFeO and NaPMoCoO strongly inhibit α-glucosidase with IC values of 6.14 ± 0.38 μM, 52.33 ± 1.41 μM, 161.90 ± 7.68 μM and 103.10 ± 2.88 μM, respectively. Moreover, HPMoO, NaPMoVO, and NaPMoCoO are reversible, competitive inhibitors with K values of 0.018 mM, 0.146 mM and 0.121 mM, respectively. NaPMoFeO inhibited α-glucosidase in a reversible noncompetitive manner with K and K of 0.312 mM and 0.412 mM, respectively. Molecular docking simulation suggested that HPMoO binds into the substrate binding site in accordance with competitive inhibition behavior and offered, in addition, an initial insight into the polypeptide-inhibitor interactions. This work presents a promising new perspective for designing effective α-glucosidase inhibitors and further demonstrates the enormous potential of polyoxomolybdates as enzyme inhibitors.