Transition Metal Substituted Polyoxometalates as α-Glucosidase Inhibitors

alpha-Glucosidase inhibitors slow the digestion of carbohydrates and reduce blood sugar levels after meals. Recently, our experimental team found that phosphomolybdic acid with a Dawson-type structure can effectively inhibit the activity of alpha-glucosidase. Dawson-type phosphomolybdic acid {H-6(P2Mo18O62), H-8[P2Mo17Fe(OH2)O-61], H-8[P2Mo17Co(OH2)O-61] and H-8[P2Mo17Ni(OH2)O-61] abbreviated as P2Mo18, P2Mo17Fe, P2Mo17Co and P2Mo17Ni} were synthesized, and their inhibitory potential for alpha-glucosidase was evaluated by enzyme kinetic analysis and molecular docking techniques. The results of kinetic analysis showed that P2Mo18, P2Mo17Fe, P2Mo17Co and P2Mo17Ni had a good inhibitory effect on alpha-glucosidase, and the inhibitor concentration values of 50 % reduction in activity were 0.174 +/- 0.0146 mu m, 0.504 +/- 0.00507 mm, 0.402 +/- 0.00381 mm, 0.293 +/- 0.0137 mm, respectively. Among them, P2Mo18, P2Mo17Co and P2Mo17Ni showed reversible mixed inhibition on alpha-glucosidase, and P2Mo17Fe showed reversible competitive inhibition on alpha-glucosidase. In addition, the four compounds separately form non-covalent interactions with the enzyme molecule, including hydrogen bonds formed, wan der vaals interactions. This result is consistent with the mechanism study of enzyme kinetics. Overall, our results indicate that Dawson-type parent P2Mo18 and three transition-metal-substituted phosphomolybdic acids P2Mo17Fe, P2Mo17Co and P2Mo17Ni are very promising as alpha-glucosidase inhibitors for the treatment of diabetes.