AUTHOR=Hu Chun-Mei , Luo Yong-Xin , Wang Wen-Jing , Li Jian-Ping , Li Meng-Yue , Zhang Yu-Fei , Xiao Di , Lu Li , Xiong Zhuang , Feng Na , Li Chen 

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

JOURNAL=Frontiers in Chemistry

VOLUME=10

YEAR=2022

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2022.926543

DOI=10.3389/fchem.2022.926543

ISSN=2296-2646

ABSTRACT=<p>Coumarin and chalcone, two important kinds of natural product skeletons, both exhibit α-glucosidase inhibitory activity. In this work, coumarin-chalcone derivatives 3 (<bold>a∼v</bold>) were synthesized, and their α-glucosidase inhibitory activity was screened. The results showed that all synthetic derivatives (IC<sub>50</sub>: 24.09 ± 2.36 to 125.26 ± 1.18 μM) presented better <italic>α</italic>-glucosidase inhibitory activity than the parent compounds 3-acetylcoumarin (IC<sub>50</sub>: 1.5 × 10<sup>5</sup> μM) and the positive control acarbose (IC<sub>50</sub>: 259.90 ± 1.06 μM). Among them, compound <bold>3t</bold> displayed the highest <italic>α</italic>-glucosidase inhibitory activity (IC<sub>50</sub>: 24.09 ± 2.36 μM), which was approximately 10 times stronger than that of acarbose. The kinetic assay of <bold>3t</bold> (<italic>K</italic><sub>I</sub> = 18.82 μM, <italic>K</italic><sub>IS</sub> = 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 <bold>3t</bold>.</p>