Study on the Antioxidant Properties of Polyoxometalates α-Glucosidase Inhibitors

Abstract

Three types of Dawson type phosphomolybdate were synthesized and the in vitro antioxidant properties of the 11 compounds were investigated by the scavenging effect of different concentrations of polyoxometalates (0～50 mg/mL with distilled water and Vitamin C (VC) as positive control, three parallel experiments were set up for each group) on 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals, hydroxyl radicals, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and superoxide anion radicals. The cytotoxicity of the compounds was assayed by methyl thiazolyl tetrazolium (MTT) assay and combined with the results of in vitro antioxidant and cytotoxicity assays, cellular antioxidant studies were performed on H6[P2Mo18O62], H7[P2Mo17VO62] and H8[P2Mo16V2O62] using HepG2 cells as a model. The total intracellular antioxidant capacity was measured using the ABTS method: 10 μL of the sample/standard solution and 200 μL of the ABTS working solution were mixed in a 96-well plate for 5 min at room temperature, and the absorbance of the sample was measured at 734 nm using a multifunctional enzyme marker. WST-1 assay for cellular superoxide dismutase (SOD) activity: The samples to be tested were diluted to different concentrations and the absorbance values were measured at 450 nm using a multifunctional enzyme marker. The SOD inhibition rate of the sample to be tested was calculated and a sample concentration of 40%～60% inhibition was selected for the experiment. Cellular antioxidant assays showed that H6[P2Mo18O62] had a total cellular antioxidant capacity comparable to that of VC at higher concentrations (25 μmol/L and above); it enhanced the activity of cellular superoxide dismutase (SOD) and was more active than VC. We investigated the interaction mechanisms of molecular docking between polyoxometalates and α-glucosidase. The results showed that all 11 compounds had good antioxidant properties, and molecular docking showed that the binding inhibition of the polyoxometalates to the amino acid residues in the active centre was reversible mainly through hydrogen bonding and van der Waals forces, and that the docking fraction was negative and the reaction could proceed spontaneously, but the types of amino acids involved varied. Among them, H6[P2Mo18O62], H8[P2Mo17Fe(OH2)O61], H8[P2Mo17Ni(OH2)O61], H7[P2Mo17VO62] and H8[P2Mo16V2O62] performed well and could be alternative materials for antioxidants with both α-glucosidase inhibiting effect.