α-Glucosidase inhibitory effect of Potentilla astracanica and some isoflavones: Inhibition kinetics and mechanistic insights through in vitro and in silico studies
α-Glucosidase inhibitory effect of Potentilla astracanica and some isoflavones: Inhibition kinetics and mechanistic insights through in vitro and in silico studies
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DOI：
10.1016/j.ijbiomac.2017.07.132
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发表时间：
2017-12-01
影响因子：
8.2
通讯作者：
Barut, Burak
中科院分区：
文献类型：
--
作者：
Sohretoglu, Didem;Sari, Suat;Barut, Burak
α-葡萄糖苷酶抑制剂临床上用于治疗2型糖尿病。我们测试了委陵菜的 α-葡萄糖苷酶抑制作用。提取物 (1, 2)，从这些提取物中分离出的两种化合物，普鲁内丁 5-O-β-吡喃葡萄糖苷 (3) 和金雀异黄素 5-O-β-吡喃葡萄糖苷 (4)，及其苷元形式（5 和 6）。与阳性对照阿卡波糖相比，所有测试材料均具有显着的α-葡萄糖苷酶抑制剂活性。金雀异黄素 (6) 显示出最高活性，IC50 值为 1.47 (+/- 0.11) mu g/ml。酶动力学分析显示3和6是非竞争性的，5是非竞争性的，4是竞争性抑制剂。使用分子建模技术，我们试图深入了解其活性的分子机制以及 6 的变构结合如何影响激动剂（麦芽糖）和酶之间的结合相互作用。 (C) 2017 Elsevier B.V. 保留所有权利。
alpha-Glucosidase enzyme inhibitors are clinically used for the treatment of Type 2 diabetes mellitus. We tested alpha-glucosidase inhibitory effects of Potentilla astracanica Jacq. extracts (1, 2), two compounds isolated from these extracts, prunetin 5-O-beta-glucopyranoside (3) and genistein 5-O-beta-glucopyranoside (4), and their aglycon forms (5 and 6). All the tested materials possessed remarkable alpha-glucosidase inhibitor activity compared to the positive control, acarbose. Genistein (6) showed the highest activity with an IC50 value of 1.47 (+/- 0.11) mu g/ml. An enzyme kinetics analysis revealed that 3 and 6 were uncompetitive, 5 was noncompetitive, and 4 was competitive inhibitors. Using molecular modeling techniques we tried to provide insight into molecular mechanisms of their activity and how allosteric binding of 6 affected binding interactions between the agonist (maltose) and the enzyme. (C) 2017 Elsevier B.V. All rights reserved.