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 (<b>a∼v</b>) 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 <i>α</i>-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 <b>3t</b> displayed the highest <i>α</i>-glucosidase inhibitory activity (IC₅₀: 24.09 ± 2.36 μM), which was approximately 10 times stronger than that of acarbose. The kinetic assay of <b>3t</b> (<i>K</i> _I = 18.82 μM, <i>K</i> _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 <b>3t</b>.