Department of Pharmacology and Experimental Therapeutics, LSUHSC, 1901 Perdido St. New Orleans, LA 70112, USA.
Bioorg Med Chem Lett. 2011 Dec 15;21(24):7379-86. doi: 10.1016/j.bmcl.2011.10.015. Epub 2011 Oct 12.
Invasive fungal infections pose a significant problem to the immune-compromised. Moreover, increased resistance to common antifungals requires development of novel compounds that can be used to treat invasive fungal infections. Naturally occurring steroidal glycosides have been shown to possess a range of functional antimicrobial properties, but synthetic methodology for their development hinders thorough exploration of this class of molecules and the structural components required for broad spectrum antifungal activity. In this report, we outline a novel approach to the synthesis of glycoside-linked functionalized 2α,3β-cholestane and spirostane molecules and present data from in vitro screenings of the antifungal activities against human fungal pathogens and as well as mammalian cell toxicity of these derivatives.
侵袭性真菌感染对免疫功能低下者构成重大问题。此外,对抗真菌药物的耐药性增加需要开发新的化合物,用于治疗侵袭性真菌感染。天然甾体糖苷已被证明具有多种功能抗菌特性,但由于其合成方法的限制,阻碍了对该类分子和广谱抗真菌活性所需的结构成分的深入探索。在本报告中,我们概述了一种合成糖苷连接的功能化 2α,3β-胆甾烷和螺甾烷分子的新方法,并介绍了这些衍生物对人源真菌病原体的抗真菌活性和对哺乳动物细胞毒性的体外筛选数据。