Hydroxycoumarin Derivatives: Novel and Potent α-Glucosidase Inhibitors
Hydroxycoumarin Derivatives: Novel and Potent α-Glucosidase Inhibitors
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DOI：
10.1021/jm100757r
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发表时间：
2010-12-09
影响因子：
7.3
通讯作者：
Gu, Lianquan
中科院分区：
文献类型：
--
作者：
Shen, Qiong;Shao, Jialiang;Gu, Lianquan
一类新的羟基香豆素衍生物被发现是有效的α -葡萄糖苷酶抑制剂。报道了它们的合成并建立了构效关系。酶动力学分析表明，化合物10是一种慢结合非竞争性抑制剂，K-i值为589 nM，而化合物11是一种竞争性抑制剂，K-i值为4.810 μ m。在所研究的羟基香豆素衍生物中，化合物10和11表现出最高的活性，是α -葡萄糖苷酶的特异性抑制剂，可以作为开发强效α -葡萄糖苷酶抑制剂的先导化合物。选择化合物10和11作为进一步探讨酶抑制机制的研究对象。
A novel class of hydroxycoumarin derivatives were found to be potent alpha-glucosidase inhibitors. Their syntheses were reported and the structure-activity relationship was established. Kinetic enzymatic assays indicated that compound 10 was a slow-binding and noncompetitive inhibitor with a K-i value of 589 nM, while compound 11 was a competitive inhibitor with a K-i value of 4.810 mu M. Among all hydroxycoumarin derivatives studied, compounds 10 and 11 exhibited the highest activities, were specific inhibitors of alpha-glucosidase, and could be exploited as the lead compounds for the development of potent alpha-glucosidase inhibitors. Compounds 10 and 11 were also selected for further discussion for the mechanism of enzymatic inhibition.