Design, synthesis and biological evaluation of novel coumarin thiazole derivatives as α-glucosidase inhibitors

作者：Wang, Guangcheng^*; He, Dianxiong; Li, Xin; Li, Juan; Peng, Zhiyun

来源：Bioorganic Chemistry, 2016, 65: 167-174.

DOI：10.1016/j.bioorg.2016.03.001

• Coumarin
• Thiazole
• alpha-Glucosidase inhibitor
• Enzyme kinetic study
• Molecular docking

A new series of coumarin thiazole derivatives 7a-7t were synthesized, characterized by H-1 NMR, C-13 NMR and element analysis, evaluated for their a-glucosidase inhibitory activity. The majority of the screened compounds displayed potent inhibitory activities with IC50 values in the range of 6.24 +/- 0.07-81.69 +/- 0.39 mu M, when compared to the standard acarbose (IC50 = 43.26 +/- 0.19 mu M). Structure-activity relationship (SAR) studies suggest that the pattern of substitution in the phenyl ring is closely related to the biological activity of this class of compounds. Among all the tested molecules, compound 7e (IC50 = 6.24 +/- 0.07 mu M) was found to be the most active compound in the library of coumarin thiazole derivatives. Enzyme kinetic studies showed that compound 7e is a non-competitive inhibitor with a K-i of 6.86 mu M. Furthermore, the binding interactions of compound 7e with the active site of alpha-glucosidase were confirmed through molecular docking. This study has identified a new class of potent a-glucosidase inhibitors for further investigation.

• 出版日期2016-4
• 单位吉首大学