Wang Guangcheng, He Dianxiong, Li Xin, Li Juan, Peng Zhiyun
College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
Bioorg Chem. 2016 Apr;65:167-74. doi: 10.1016/j.bioorg.2016.03.001. Epub 2016 Mar 2.
A new series of coumarin thiazole derivatives 7a-7t were synthesized, characterized by (1)H NMR, (13)C NMR and element analysis, evaluated for their α-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±0.39μM, when compared to the standard acarbose (IC50=43.26±0.19μM). 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±0.07μM) 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 Ki of 6.86μM. Furthermore, the binding interactions of compound 7e with the active site of α-glucosidase were confirmed through molecular docking. This study has identified a new class of potent α-glucosidase inhibitors for further investigation.
合成了一系列新的香豆素噻唑衍生物7a - 7t，通过¹H NMR、¹³C NMR和元素分析对其进行表征，并评估了它们的α - 葡萄糖苷酶抑制活性。与标准阿卡波糖（IC50 = 43.26±0.19μM）相比，大多数筛选出的化合物表现出较强的抑制活性，IC50值在6.24±0.07 - 81.69±0.39μM范围内。构效关系（SAR）研究表明，苯环上的取代模式与这类化合物的生物活性密切相关。在所有测试分子中，化合物7e（IC50 = 6.24±0.07μM）被发现是香豆素噻唑衍生物库中活性最高的化合物。酶动力学研究表明，化合物7e是一种非竞争性抑制剂，Ki为6.86μM。此外，通过分子对接证实了化合物7e与α - 葡萄糖苷酶活性位点的结合相互作用。本研究确定了一类新的强效α - 葡萄糖苷酶抑制剂以供进一步研究。
