Discovery of potent α-glucosidase inhibitor flavonols: Insights into mechanism of action through inhibition kinetics and docking simulations

Beside other pharmaceutical benefits, flavonoids are known for their potent a-glucosidase inhibition. In the present study, we investigated alpha-glucosidase inhibitory effects of structurally related 11 flavonols, among which quercetin-3-O-(3 ''-O-galloyl)-beta-galactopyranoside (8) and quercetin 3-O-(6 ''-O-galloyl)-beta-glucopyranoside (9) showed significant inhibition compared to the positive control, acarbose, with IC50 values of 0.97 +/- 0.02 and 1.35 +/- 0.06 mu M, respectively. It was found that while sugar substitution to C3-OH of C ring reduced the alpha-glucosidase inhibitory effect, galloyl substitution to these sugar units increased it. An enzyme kinetics analysis revealed that 7 was competitive, whereas 1, 2, 8, and 9 were uncompetitive inhibitors. In the light of these findings, we performed molecular docking studies to predict their inhibition mechanisms at atomic level.