Synthesis and Evaluation of Coumarin-Chalcone Derivatives as α-Glucosidase Inhibitors.

ABSTRACT

Coumarin and chalcone, two important kinds of natural product skeletons, both exhibit α-glucosidase inhibitory activity. In this work, coumarin-chalcone derivatives 3 (a∼v) were synthesized, and their α-glucosidase inhibitory activity was screened. The results showed that all synthetic derivatives (IC50 24.09 ± 2.36 to 125.26 ± 1.18 µM) presented better α-glucosidase inhibitory activity than the parent compounds 3-acetylcoumarin (IC50 1.5 × 105 µM) and the positive control acarbose (IC50 259.90 ± 1.06 µM). Among them, compound 3t displayed the highest α-glucosidase inhibitory activity (IC50 24.09 ± 2.36 µM), which was approximately 10 times stronger than that of acarbose. The kinetic assay of 3t (K I = 18.82 µM, K IS = 59.99 µM) revealed that these compounds inhibited α-glucosidase in a mixed-type manner. Molecular docking was used to simulate the interaction between α-glucosidase and compound 3t.