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锥虫硫醇还原酶:抗锥虫和抗利什曼原虫药物设计的一个可行化疗靶点。

Trypanothione reductase: a viable chemotherapeutic target for antitrypanosomal and antileishmanial drug design.

作者信息

Khan M Omar F

机构信息

College of Pharmacy, Southwestern Oklahoma State University, 100 Campus Drive, Weatherford, OK 73096, U.S.A.

出版信息

Drug Target Insights. 2007;2:129-46. Epub 2007 Jun 19.

Abstract

Trypanosomiasis and leishmaniasis are two debilitating disease groups caused by parasites of Trypanosoma and Leishmania spp. and affecting millions of people worldwide. A brief outline of the potential targets for rational drug design against these diseases are presented, with an emphasis placed on the enzyme trypanothione reductase. Trypanothione reductase was identified as unique to parasites and proposed to be an effective target against trypanosomiasis and leishmaniasis. The biochemical basis of selecting this enzyme as a target, with reference to the simile and contrast to human analogous enzyme glutathione reductase, and the structural aspects of its active site are presented. The process of designing selective inhibitors for the enzyme trypanothione reductase has been discussed. An overview of the different chemical classes of inhibitors of trypanothione reductase with their inhibitory activities against the parasites and their prospects as future chemotherapeutic agents are briefly revealed.

摘要

锥虫病和利什曼病是由锥虫属和利什曼原虫属寄生虫引起的两类使人虚弱的疾病,影响着全球数百万人。本文简要概述了针对这些疾病进行合理药物设计的潜在靶点,重点介绍了锥虫硫醇还原酶。锥虫硫醇还原酶被确定为寄生虫所特有的酶,并被认为是对抗锥虫病和利什曼病的有效靶点。本文介绍了选择该酶作为靶点的生化基础,参考了其与人类类似酶谷胱甘肽还原酶的异同,以及其活性位点的结构方面。讨论了设计锥虫硫醇还原酶选择性抑制剂的过程。简要介绍了锥虫硫醇还原酶抑制剂的不同化学类别及其对寄生虫的抑制活性以及作为未来化疗药物的前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/204d/3155241/4cfac5a85b33/dti-2-2007-129f1.jpg

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