以锥虫硫酮还原酶为靶点的抗锥虫和抗利什曼原虫药物先导物的合理药物设计。

Drug design and discovery Pub Date : 1999-07-01
S E Austin, M O Khan, K T Douglas
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引用次数: 0

摘要

在一些实验室中,寄生虫酶锥虫硫酮还原酶已被用作合理设计抗锥虫病和利什曼病药物的靶点。本文综述了其作为靶点的生物化学基础。然后将靶标的相关结构方面与在哺乳动物宿主中发现的同源结构进行比较,以表明可能实现选择性毒性的分子基础。提供了已知抑制剂类别的概述,准备详细介绍获得强选择性抑制剂的方法,并概述了通过相互作用分子图形配体设计初步发现三环结构的过程中所采取的步骤。本文还介绍了近年来应用于该系统的定量对接方法。最后,总结了在体外和体内抗各种寄生虫活性的生物学数据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Rational drug design using trypanothione reductase as a target for anti-trypanosomal and anti-leishmanial drug leads.

The parasite enzyme trypanothione reductase has been used as a target for rational drug design against trypanosomiasis and leishmaniasis in a number of laboratories. In this article the biochemical basis for its selection as a target is reviewed. The relevant structural aspects of the target are then compared with the homologous structure found in the mammalian hosts to indicate the molecular basis by which selective toxicity is likely to be achieved. An overview of known classes of inhibitors is provided, preparatory to a detailed coverage of approaches that have been taken to obtaining strong, selective inhibitors and the steps taken in the process of the initial discovery of tricyclic structures by interactive molecular graphics ligand design are outlined. Recent quantitative docking approaches which have been applied to this system are also described. Finally, the biological data of the activity against the various parasitic forms in vitro and in vivo are summarised.

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