Inhibition of Aquaporin 4 by antiepileptic drugs

被引：104

作者：

Huber, Vincent J. ^{[1
]}

Tsujita, Mika ^{[1
]}

Kwee, Ingrid L. ^{[2
]}

Nakada, Tsutomu ^{[1
,2
]}

机构：

[1] Niigata Univ, Brain Res Inst, Ctr Integrated Human Brain Sci, Niigata 9518585, Japan

[2] Univ Calif Davis, Dept Neurol, Davis, CA 95616 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2009年 / 17卷 / 01期

关键词：

Aquaporin; 4; Antiepileptic drugs; Drug design; Xenopus laevis oocytes; WATER CHANNEL; BRAIN-TUMORS; EXPRESSION; MICE; EPILEPSY; EDEMA; PERMEABILITY; HIPPOCAMPUS; MENINGITIS; TRANSPORT;

D O I：

10.1016/j.bmc.2007.12.038

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

The potential of antiepileptic drugs (AEDs) to inhibit the water transport properties of Aquaporin 4 (AQP4) was investigated using a combination of in silico and in vitro screening methods. Virtual docking studies on 14 AEDs indicated a range of docking energies that spanned approximately 40 kcal/mol, where the most stabilized energies were consistent with that of the previously identified AQP4 inhibitor acetazolamide. Nine AEDs and one bio-active metabolite were further investigated in a functional assay using AQP4 expressing Xenopus oocytes. Seven of the assayed compounds were found to inhibit AQP4 function, while three did not. A linear correlation was indicated between the in silico docking energies and the in vitro AQP4 inhibitory activity at 20 mu M. (C) 2007 Elsevier Ltd. All rights reserved.

引用

页码：418 / 424

页数：7

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