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抗线粒体抗真菌测定法在新药的发现和开发中的应用。

The anti-mitochondrial antifungal assay for the discovery and development of new drugs.

机构信息

University of the Free State, Department of Microbial , Biochemical and Food Biotechnology, Bloemfontein , South Africa +27514012249 ; +27514019376 ;

出版信息

Expert Opin Drug Discov. 2011 Jun;6(6):671-81. doi: 10.1517/17460441.2011.575358. Epub 2011 Apr 14.

Abstract

INTRODUCTION

New targets and drugs are constantly searched for to effectively combat fungal infections and diseases such as cancer. Mitochondria, as the main powerhouses of eukaryotic cells, must be regarded as important targets for the development of new therapies. This has lead to the development of a fungal assay that shows potential in the selection of new antifungal and anticancer drugs as well as the identification of compounds that are toxic to human mitochondria.

AREAS COVERED

In this review the authors discuss the development of a potential method of drug discovery that targets mitochondrial function. The authors cover the application of new nanotechnology as well as fungal systematic research where the link between fungal fruiting structures, cell growth, increased mitochondrial activity and susceptibility to a variety of anti-mitochondrial drugs is assessed.

EXPERT OPINION

This assay shows potential to select anti-mitochondrial drugs as a first screen. This should be followed up by more specific in vitro and in vivo tests to pinpoint the type of anti-mitochondrial activity exerted by these drugs, if any. This is because the possibility exists that compounds regarded as anti-mitochondrial may not inhibit mitochondrial function but other fruiting structure developmental stages and therefore yield false positives. To enhance our knowledge on how these drugs act at the structural level, the authors recommend Nano Scanning Auger Microscopy as the tool of choice.

摘要

简介

为了有效对抗真菌感染和癌症等疾病,人们一直在不断寻找新的靶点和药物。线粒体作为真核细胞的主要“动力源”,必须被视为开发新疗法的重要靶点。这促使人们开发了一种真菌检测方法,该方法有望用于选择新的抗真菌和抗癌药物,并鉴定对人线粒体有毒的化合物。

涵盖领域

本文作者讨论了一种靶向线粒体功能的药物发现的潜在方法。作者介绍了纳米技术的新应用,以及真菌系统研究,其中评估了真菌子实体、细胞生长、线粒体活性增加与多种抗线粒体药物敏感性之间的联系。

专家意见

该检测方法显示出作为初步筛选选择抗线粒体药物的潜力。这应该通过更具体的体外和体内试验来跟进,以确定这些药物所发挥的抗线粒体活性的类型(如果有的话)。因为有可能存在被认为是抗线粒体的化合物实际上并不抑制线粒体功能,而是其他子实体发育阶段,从而产生假阳性。为了增强我们对这些药物在结构水平上如何作用的了解,作者建议使用纳米扫描俄歇显微镜作为首选工具。

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