Synthesis and Evaluation of Coumarin-Chalcone Derivatives as alpha-Glucosidase Inhibitors

Coumarin and chalcone, two important kinds of natural product skeletons, both exhibit alpha-glucosidase inhibitory activity. In this work, coumarin-chalcone derivatives 3 (a & SIM;v) were synthesized, and their alpha-glucosidase inhibitory activity was screened. The results showed that all synthetic derivatives (IC50: 24.09 +/- 2.36 to 125.26 +/- 1.18 mu M) presented better alpha-glucosidase inhibitory activity than the parent compounds 3-acetylcoumarin (IC50: 1.5 x 10(5) mu M) and the positive control acarbose (IC50: 259.90 +/- 1.06 mu M). Among them, compound 3t displayed the highest alpha-glucosidase inhibitory activity (IC50: 24.09 +/- 2.36 mu M), which was approximately 10 times stronger than that of acarbose. The kinetic assay of 3t (K (I) = 18.82 mu M, K (IS) = 59.99 mu M) revealed that these compounds inhibited alpha-glucosidase in a mixed-type manner. Molecular docking was used to simulate the interaction between alpha-glucosidase and compound 3t.