Transition Metal Substituted Polyoxometalates as α‐Glucosidase Inhibitors

α‐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 α‐glucosidase. Dawson‐type phosphomolybdic acid {H6(P2Mo18O62), H8[P2Mo17Fe(OH2)O61], H8[P2Mo17Co(OH2)O61] and H8[P2Mo17Ni(OH2)O61] abbreviated as P2Mo18, P2Mo17Fe, P2Mo17Co and P2Mo17Ni} were synthesized, and their inhibitory potential for α‐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 α‐glucosidase, and the inhibitor concentration values of 50 % reduction in activity were 0.174 ± 0.0146 µm, 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 α‐glucosidase, and P2Mo17Fe showed reversible competitive inhibition on α‐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 α‐glucosidase inhibitors for the treatment of diabetes. The Dawson‐type parent P2Mo18 and three transition‐metal‐substituted compounds P2Mo17Fe, P2Mo17Co, and P2Mo17Ni were synthesized and characterized. We evaluated their potential to inhibit α‐glucosidase and found that all four compounds had significant inhibitory effects, P2Mo18 being the best among them. The four compounds separately have non‐covalent interactions with the enzyme molecule.