Chiang Mai Journal of Science

     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.