Structural analysis of compounds withactions similar to local anesthetics andantipsychotic phenothiazines in yeast
Structural analysis of compounds withactions similar to local anesthetics andantipsychotic phenothiazines in yeast
复制标题
酵母中具有类似局麻药和抗精神病药吩噻嗪类作用的化合物的结构分析
DOI：
10.1002/yea.1846
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发表时间：
2011
期刊：
影响因子：
2.6
通讯作者：
Ichiro Terashima
中科院分区：
文献类型：
--
作者：
Yukifumi Uesono;Akio Toh-e;YoshikoKikuchi;Ichiro Terashima
局部麻醉剂和抗精神病药物吩噻嗪类药物会导致酵母细胞中肌动蛋白极化和翻译起始的快速关闭，就像一些环境压力一样。这些化合物都具有两亲性结构、表面活性剂活性和裂解酵母细胞的能力。为了阐明负责关闭活动和细胞裂解的结构，我们研究了各种两亲物。在疏水区，直链烷基结构足以关闭肌动蛋白极化和翻译起始。在直链烷基化合物的亲水区域，阳离子三甲基铵（TMA）和非离子羟基结构（醇）关闭了这两个反应，而具有长烷基链（≥C6）的阴离子结构硫酸盐仅关闭了肌动蛋白极化。在关闭两个反应的化合物上，包括临床药物、TMA化合物和醇，关闭和裂解的效力随着疏水区域中碳的数目的增加而指数地增加，而安全性受亲水和疏水区域的结构的影响。这些结果表明，酵母系统可以很容易地评估临床药物，并为设计化合物关闭细胞内反应提供了结构基础。版权所有© 2011约翰威利父子有限公司.
Local anesthetics and antipsychotic phenothiazines cause a rapid shutdown of both actin polarization and translation initiation in yeast cells, like some environmental stresses. These compounds all have an amphiphilic structure, surfactant activity and the ability to lyse yeast cells. To elucidate the structures responsible for the shutdown activity and cell lysis, we investigated a variety of amphiphiles. In the hydrophobic region, the straight alkyl structure was sufficient for the shutdown of actin polarization and translational initiation. In the hydrophilic region of the straight alkyl compounds, cationic trimethyl ammonium (TMA) and non‐ionic hydroxyl structure (alcohols) shut down both reactions, while an anionic structure, sulphate, with a long alkyl chain (≥C6) shut down actin polarization only. On the compounds that shut down both reactions, including the clinical drugs, TMA compounds and alcohols, the potencies of shutdown and lysis exponentially increased with increasing the number of carbons in the hydrophobic region, whereas safety was affected by the structures of both hydrophilic and hydrophobic regions. These results indicate that the yeast system can easily evaluate clinical drugs, and provide a structural basis for designing compounds to shut down intracellular reactions. Copyright © 2011 John Wiley & Sons, Ltd.