The Activity And Structural Effection Of Hesperetin And 2-thiobarbituric On α-glucosidase

Researches ofα-glucosidase inhibitor have attracted the attention of researchers due to its association to type II diabetes treatment in humans.In this research,the effects mechanism of hesperetin and 2-thiobarbituric acid onα-glucosidase activity were evaluated by combining inhibition kinetics and molecular docking simulations.The results showed that hesperetin reversibly inhibitedα-glucosidase(IC₅₀=0.38±0.05 mM;K_islope=0.23±0.01 mM)in a parabolic mixed manner,which was accompanied by tertiary structural changes of the enzyme.Based on computational molecular dynamics and docking simulations,hesperetin interacts with several residues near the active site ofα-glucosidase（eg.Lys155,Asn241,Glu304,Pro309,Phe311,and Arg312）.2-Thiobarbituric acid reversibly inhibitsα-glucosidase(IC₅₀=17.13±1.14 mM,K_islope=13.25±0.56 mM)in a parabolic noncompetitive inhibitory manner,which was accompanied by a biphasic kinetic process.However,the tertiary structural changes of the enzyme are not synchronized with the inhibition of 2-thiobarbituric acid,and the hydrophobicity of the enzyme can be observed with the action of higher concentration of 2-thiobarbituric acid.The results of this study come up with the viewpoints of the combinding and inhibiting mechanism of hesperetin and 2-thiobarbituric acid residues located at the active sites ofα-glucosidase.And it is suggested that hesperetin could be used as a potential therapeutic agent for treatingα-glucosidase-associated type II diabetes.And 2-thiobarbituric acid could be used as a probe,with which compounds similar to TBA（heterocyclic compounds）targeting the key residues of active sites are potentialα-glucosidase inhibitors.