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功能化 2,3-螺甾烷异构体的合成及抗真菌活性。

Synthesis and antifungal activity of functionalized 2,3-spirostane isomers.

机构信息

Department of Chemistry, University of New Orleans, New Orleans, LA 70148, USA.

出版信息

Bioorg Med Chem Lett. 2011 May 15;21(10):2826-31. doi: 10.1016/j.bmcl.2011.03.092. Epub 2011 Mar 30.

Abstract

Invasive fungal infections are a major complication for individuals with compromised immune systems. One of the most significant challenges in the treatment of invasive fungal infections is the increased resistance of many organisms to widely used antifungals, making the development of novel antifungal agents essential. Many naturally occurring products have been found to be effective antimicrobial agents. In particular, saponins with spirostane glycosidic moieties-isolated from plant or marine species-have been shown to possess a range of antimicrobial properties. In this report, we outline a novel approach to the synthesis of a number of functionalized spirostane molecules that can be further used as building blocks for novel spirostane-linked glycosides and present results from the in vitro screenings of the antifungal potential of each derivative against four fungal species, including Candida albicans, Cryptococcus neoformans, Candida glabrata, and the filamentous fungus Aspergillus fumigatus.

摘要

侵袭性真菌感染是免疫系统受损个体的主要并发症之一。治疗侵袭性真菌感染的最大挑战之一是许多生物体对广泛使用的抗真菌药物的耐药性增加,因此开发新型抗真菌药物至关重要。已经发现许多天然存在的产物是有效的抗菌剂。特别是,从植物或海洋物种中分离出的具有螺甾烷糖苷部分的皂苷已被证明具有一系列抗菌特性。在本报告中,我们概述了一种合成多种功能化螺甾烷分子的新方法,这些分子可以进一步用作新型螺甾烷连接的糖苷的构建块,并介绍了针对四种真菌物种(包括白色念珠菌、新型隐球菌、近平滑念珠菌和丝状真菌烟曲霉)对每个衍生物的抗真菌潜力进行体外筛选的结果。

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