Hacettepe University, Faculty of Pharmacy, Department of Pharmacognosy, Sıhhiye, TR-06100 Ankara, Turkey.
Hacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Sıhhiye, TR-06100 Ankara, Turkey.
Bioorg Chem. 2018 Sep;79:257-264. doi: 10.1016/j.bioorg.2018.05.010. Epub 2018 May 17.
Beside other pharmaceutical benefits, flavonoids are known for their potent α-glucosidase inhibition. In the present study, we investigated α-glucosidase inhibitory effects of structurally related 11 flavonols, among which quercetin-3-O-(3″-O-galloyl)-β-galactopyranoside (8) and quercetin 3-O-(6″-O-galloyl)-β-glucopyranoside (9) showed significant inhibition compared to the positive control, acarbose, with IC values of 0.97 ± 0.02 and 1.35 ± 0.06 µM, respectively. It was found that while sugar substitution to C3-OH of C ring reduced the α-glucosidase inhibitory effect, galloyl substitution to these sugar units increased it. An enzyme kinetics analysis revealed that 7 was competitive, whereas 1, 2, 8, and 9 were uncompetitive inhibitors. In the light of these findings, we performed molecular docking studies to predict their inhibition mechanisms at atomic level.
除了其他药物益处外，类黄酮还因其具有很强的α-葡萄糖苷酶抑制作用而闻名。在本研究中，我们研究了结构相关的 11 种黄酮醇的α-葡萄糖苷酶抑制作用，其中槲皮素-3-O-(3″-O-没食子酰基)-β-半乳糖吡喃糖苷（8）和槲皮素 3-O-(6″-O-没食子酰基)-β-葡萄糖吡喃糖苷（9）与阳性对照阿卡波糖相比表现出显著的抑制作用，IC 值分别为 0.97±0.02 和 1.35±0.06µM。结果发现，C 环上 C3-OH 的糖取代会降低α-葡萄糖苷酶抑制作用，而这些糖单元的没食子酰基取代则会增加其抑制作用。酶动力学分析表明，7 是竞争性抑制剂，而 1、2、8 和 9 是反竞争性抑制剂。根据这些发现，我们进行了分子对接研究，以在原子水平上预测它们的抑制机制。
