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

Abstract

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 H₃PMo₁₂O₄₀, Na₄PMo₁₁VO₄₀, Na₆PMo₁₁FeO₄₀ and Na₇PMo₁₁CoO₄₀ strongly inhibit α-glucosidase with IC₅₀ 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, H₃PMo₁₂O₄₀, Na₄PMo₁₁VO₄₀, and Na₇PMo₁₁CoO₄₀ are reversible, competitive inhibitors with K_I values of 0.018 mM, 0.146 mM and 0.121 mM, respectively. Na₆PMo₁₁FeO₄₀ inhibited α-glucosidase in a reversible noncompetitive manner with K_I and K_IS of 0.312 mM and 0.412 mM, respectively. Molecular docking simulation suggested that H₃PMo₁₂O₄₀ 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.

Keywords: Enzyme kinetics; Molecular docking; Polyoxomolybdates (POMs); α-Glucosidase inhibitors.