Quantum mechanics

Polyphenol

Myricetin

Non-competitive inhibition

Binding constant

Receptor

Biochemistry

Stereochemistry

Quenching (fluorescence)

Catechin

Physics

Binding site

Antioxidant

Enzyme

Fluorescence

Kaempferol

Flavonoid

Uncompetitive inhibitor

Chemistry

Quercetin

Dissociation constant

Bioorganic Chemistry

α-Glucosidase inhibition of 11 flavonoids, including myricetins, quercetins and catechins were studied through initial reaction velocity, IC50 value, inhibition kinetics, fluorescence quenching and molecular docking. It was found that C4 = O, C2 = C3, 3-OH and 5'-OH were essential moieties for α-glucosidase inhibition of myricetin that was shown with the highest inhibitory activity. The trans-conformational catechins was shown with stronger inhibition effects than the cis-conformational ones. Further, gallocatechin was an uncompetitive inhibitor, while myricetin, myricetrin, quercetin and catechin were competitive ones. 3-OH and 5'-OH promoted myricetin to bind with the enzyme active site through hydrogen bondings. The presence of C4 = O and C2 = C3 increased electron delocalization in ring A-C for myricetin and quercetin, and this enhanced stability of π-conjugations with aromatic residues of amino acids. However, 5'-OH decreased the quenching effects because it limited π-conjugations of ring B with key fluorescent residues. Notably, for same flavonoid sort, the constants that indicate binding affinity of flavonoids to α-glucosidase, including reciprocal of competitive inhibition constant, fluorescence quenching constant and binding energy followed same order as the inhibitory activity, indicating that α-glucosidase inhibition of the flavonoids resulted from binding interactions between them, and that the methods above can be combined reasonably to characterize flavonoid-enzyme binding interactions.

Essential moieties of myricetins, quercetins and catechins for binding and inhibitory activity against α-Glucosidase