Transition Metal Substituted Polyoxometalates as α‐Glucosidase Inhibitors

Abstract

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 {H 6 (P 2 Mo 18 O 62 ), H 8 [P 2 Mo 17 Fe(OH 2 )O 61 ], H 8 [P 2 Mo 17 Co(OH 2 )O 61 ] and H 8 [P 2 Mo 17 Ni(OH 2 )O 61 ] abbreviated as P 2 Mo 18 , P 2 Mo 17 Fe, P 2 Mo 17 Co and P 2 Mo 17 Ni} 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 P 2 Mo 18 , P 2 Mo 17 Fe, P 2 Mo 17 Co and P 2 Mo 17 Ni had a good inhibitory effect on α‐glucosidase, and the inhibitor concentration values of 50 % reduction in activity were 0.174 ± 0.0146 µ m , 0.504 ± 0.00507 m m , 0.402 ± 0.00381 m m , 0.293 ± 0.0137 m m , respectively. Among them, P 2 Mo 18 , P 2 Mo 17 Co and P 2 Mo 17 Ni showed reversible mixed inhibition on α‐glucosidase, and P 2 Mo 17 Fe 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 P 2 Mo 18 and three transition‐metal‐substituted phosphomolybdic acids P 2 Mo 17 Fe, P 2 Mo 17 Co and P 2 Mo 17 Ni are very promising as α‐glucosidase inhibitors for the treatment of diabetes.