Hydrophobic Binding and Inhibition Mechanism of 2,3-Dihydroxychalcones against α-Glucosidase

In continuation of our interest in fluorinated chalcones with promising bioactivities, four 2,3-dihydroxychalcones named Non-F, 3-F, 4-F and 3,4-diF were screened for their α-glucosidase inhibitory activity. All tested four compounds exhibited better inhibitory activities than the positive reference control, acarbose (IC50 = 69.582.04 µM). Remarkably, compounds 3,4-diF (IC50 = 5.340.11 µM) and 3-F (IC50 = 6.840.33 µM) demonstrated more than 10-fold greater potency in α-glucosidase inhibition than acarbose in our assay. Intrinsic fluorescence quenching measurements revealed that the inhibitors directly bind to α-glucosidase. The fluorescence intensity of [α-glucosidase/8-anilino-1-naphthalenesulfonic acid (ANS)] complexes was quenched upon addition of inhibitors, indicating hydrophobic contacts between enzyme and fluorinated chalcones. Furthermore, the Lineweaver-Burk plots were applied to determine the inhibition mechanisms of chalcones against α-glucosidase. For the first time, it was found that Non-F, 4-F and 3,4-diF are competitive inhibitors, whereas 3-F acts as a non-competitive inhibitor.