Antifungal activity of 2α,3β-functionalized steroids stereoselectively increases with the addition of oligosaccharides

• Published in: Bioorganic & medicinal chemistry letters 2011-12, Vol.21 (24), p.7379-7386
• Main Authors: Cammarata, Amy, Upadhyay, Sunil Kumar, Jursic, Branko S., Neumann, Donna M.
• Format: Article
• Language: English
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal; Antifungal agents; Antifungal Agents - chemical synthesis; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; antifungal properties; Biological and medical sciences; chemistry; Cholestanes; Cholestanes - chemistry; fungi; Fungi - drug effects; Glycosides; Glycosides - chemical synthesis; Glycosides - chemistry; Glycosides - pharmacology; Humans; Medical sciences; Microbial Sensitivity Tests; oligosaccharides; Oligosaccharides - chemistry; pathogens; Pharmacology. Drug treatments; Spirostanes; Spirostans - chemistry; Stereoisomerism; steroids; Steroids - chemistry; toxicity
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2011.10.015

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.