Inhibition of Aquaporin 4 by antiepileptic drugs
Inhibition of Aquaporin 4 by antiepileptic drugs
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DOI：
10.1016/j.bmc.2007.12.038
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发表时间：
2009-01-01
影响因子：
3.5
通讯作者：
Nakada, Tsutomu
中科院分区：
文献类型：
--
作者：
Huber, Vincent J.;Tsujita, Mika;Nakada, Tsutomu
采用计算机模拟和体外筛选相结合的方法研究了抗癫痫药物（AEDs）对水通道蛋白4（AQP4）水转运特性的抑制潜力。对14种抗癫痫药物进行的虚拟对接研究表明，对接能的范围约为40千卡/摩尔，其中最稳定的能量与先前确定的水通道蛋白4抑制剂乙酰唑胺的能量一致。在使用表达水通道蛋白4的非洲爪蟾卵母细胞进行的功能测定中，进一步研究了9种抗癫痫药物和一种生物活性代谢物。在所检测的化合物中，有7种被发现抑制水通道蛋白4的功能，而3种没有。计算机模拟对接能与20μM浓度下的体外水通道蛋白4抑制活性之间呈线性相关。（C）2007爱思唯尔有限公司。保留所有权利。
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.