Structural Modeling and Identification of Imperatorin as Novel L-type Calcium Channel Blocker
Structural Modeling and Identification of Imperatorin as Novel L-type Calcium Channel Blocker
复制标题
新型 L 型钙通道阻滞剂欧前胡素的结构建模和鉴定
DOI：
10.2174/1573406411309070013
复制
发表时间：
2013-11-01
影响因子：
2.3
通讯作者：
Zhang, Jie
中科院分区：
文献类型：
--
作者：
Lu, Wen;Zhang, Tao;Zhang, Jie
L型钙通道（LTCC）阻滞剂用作心脏抗心律失常药或抗高血压药。在我们以前的研究中，我们已经报道了一种呋喃香豆素，欧前胡素，它表现出强大的血管扩张作用。其作用机制可能与抑制LTCC有关。为了进一步研究欧前胡素与LTCC相互作用的药理机制，采用MODELLER 9.9程序以钾通道为模板对LTCC进行同源模建。通过分子对接进一步研究了欧前胡素与LTCC的结合方式。分子对接结果表明，欧前胡素与维拉帕米占据相同的结合位点，氢键作用在阻断剂-通道结合中起重要作用。对接研究为了解欧前胡素的作用机制提供了有用的信息。本文的研究结果将有助于开发新型LTCC阻滞剂。
L-type calcium channel (LTCC) blockers are used as cardiac antiarrhythmics or antihypertensives. In our previous research, we have reported a furanocoumarin, imperatorin, which exhibited potent vasodilatory effects. The possible mechanism might involve with inhibition against LTCC. In order to further investigate the pharmacologic mechanism of imperatorin for interaction with LTCC, the homology modeling of LTCC was performed using MODELLER 9.9 program with potassium channels as templates. The binding mode of imperatorin to LTCC was further investigated by molecular docking. Molecular docking results indicated that imperatorin occupied the same binding site as verapamil and hydrogen bond interaction played important role in blocker-channel binding. Docking studies provided useful information to understand the action mechanism of imperatorin. The results described here will be helpful in the development of novel potential LTCC blockers.