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新型小分子药物治疗白念珠菌感染的专利研究(2002-2010)

Novel small molecules for the treatment of infections caused by Candida albicans: a patent review (2002-2010).

机构信息

University of Florence, Department of Chemistry Ugo Schiff, Polo Scientifico e Tecnologico, Via della Lastruccia 13, I-50019 Sesto Fiorentino, Florence, Italy.

出版信息

Expert Opin Ther Pat. 2011 Mar;21(3):381-97. doi: 10.1517/13543776.2011.551116. Epub 2011 Jan 18.

Abstract

INTRODUCTION

The fungal pathogen Candida albicans is one of the leading causes of infections affecting immunodeficient individuals, including those HIV-infected and patients undergoing cancer therapy. Emerging problems in terms of therapeutic efficacy and drug resistance have highlighted the need to consider new therapeutic approaches, based on the exploitation of virulence factors as alternatives to conventional drug targets.

AREAS COVERED

Advances in the development of anti-Candida drugs are examined in this review, as reflected by the patent literature since 2002 along with selected peer-reviewed publications. Taking into account a total of 26 patents, the discussion encompasses several therapeutic approaches, including azoles as ergosterol biosynthesis inhibitors, glucan and chitin synthase inhibitors, and secreted aspartyl protease inhibitors.

EXPERT OPINION

New analogs of existing drugs are being developed as broad spectrum antifungals to improve efficacy and circumvent drug resistance. Also, candidate drugs targeting new virulence factors are promising to overcome limitations due to poor efficacy and the rising of drug resistance observed for several available drugs. Efforts for the discovery and development of antifungal agents should be equivalent to other therapeutic areas, and advances in the generation of therapeutic agents with fungus-specific mechanisms of action are of highest priority.

摘要

简介

真菌病原体白色念珠菌是影响免疫功能低下个体(包括 HIV 感染者和接受癌症治疗的患者)感染的主要原因之一。在治疗效果和耐药性方面出现的新问题,突出表明需要考虑新的治疗方法,即利用毒力因子作为传统药物靶点的替代品。

涵盖领域

本综述考察了自 2002 年以来专利文献以及部分同行评议出版物中反映的抗真菌药物的发展情况。考虑到总共 26 项专利,讨论涵盖了几种治疗方法,包括作为麦角甾醇生物合成抑制剂的唑类药物、葡聚糖和几丁质合成酶抑制剂以及分泌天冬氨酸蛋白酶抑制剂。

专家意见

正在开发现有药物的新类似物作为广谱抗真菌药,以提高疗效并避免耐药性。此外,针对新毒力因子的候选药物有望克服现有药物疗效不佳和耐药性上升带来的限制。对抗真菌药物的发现和开发的努力应与其他治疗领域相当,具有真菌特异性作用机制的治疗药物的进展应是重中之重。

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