Structure-activity relationships of dibenzoylhydrazines for the inhibition of P-glycoprotein-mediated quinidine transport
Structure-activity relationships of dibenzoylhydrazines for the inhibition of P-glycoprotein-mediated quinidine transport
复制标题
DOI：
10.1016/j.bmc.2016.05.039
复制
发表时间：
2016-07-15
影响因子：
3.5
通讯作者：
Akamatsu, Miki
中科院分区：
文献类型：
--
作者：
Miyata, Ken-ichi;Nakagawa, Yoshiaki;Akamatsu, Miki
我们以前证明，二苯甲酰肼（DBH）不仅是P-糖蛋白（P-gp）的底物，而且是抑制剂。在本研究中，我们评估了抑制P-gp介导的奎尼丁运输的两个系列的DBH和进行了经典的QSAR分析和对接模拟，以调查的机制P-gp底物/抑制剂识别。定量构效关系分析的结果表明，疏水因子是抑制活性的最重要因素，而电子和空间效应也会影响活性。不同系列中观察到的不同取代基效应表明，不同系列的DBH，这是支持的对接模拟结果的结合模式。(C)2016爱思唯尔有限公司版权所有
We previously demonstrated that dibenzoylhydrazines (DBHs) are not only P-glycoprotein (P-gp) substrates, but also inhibitors. In the present study, we evaluated the inhibition of P-gp-mediated quinidine transport by two series of DBHs and performed a classical QSAR analysis and docking simulation in order to investigate the mechanisms underlying P-gp substrate/inhibitor recognition. The results of the QSAR analysis identified the hydrophobic factor as the most important for inhibitory activities, while electronic and steric effects also influenced the activities. The different substituent effects observed in each series suggested the different binding modes of each series of DBHs, which was supported by the results of the docking simulation. (C) 2016 Elsevier Ltd. All rights reserved.