Fungal ABC Transporter-Associated Activity of Isoflavonoids from the Root Extract of Dalea formosa

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• 作者：Gil Belofsky ; Marcin Kolaczkowski ; Earle Adams ; John Schreiber ; Victoria Eisenberg ; Christina M. Coleman ; Yike Zou ; Daneel Ferreira
• 刊名：Journal of Natural Products
• 出版年：2013
• 出版时间：May 24, 2013
• 年：2013
• 卷：76
• 期：5
• 页码：915-925
• 全文大小：405K
• 年卷期：v.76,no.5(May 24, 2013)
• ISSN：1520-6025

文摘

New potential treatments for disseminated fungal infections are needed, especially for infections caused by the commonly drug-resistant pathogens Candida albicans and C. glabrata. These pathogens cause systemic candidiasis, a significant cause of mortality in immune-compromised patients. ABC transporters of the pleiotropic drug resistance subfamily, such as Cdr1p of C. albicans, play an important role in antifungal resistance and are potential bioassay targets for antifungal therapies against drug-resistant pathogens. We observed strong antifungal growth inhibitory activity in the methanol extract of Dalea formosa roots. This extract afforded six new isoflavonoids, sedonans A鈥揊 (1鈥?b>6), a new but-2-enolide, 4鈥?O-methylpuerol A (7), and the new pterocarpan ent-sandwicensin (8). The structures and absolute configurations of these compounds were assigned using spectroscopic and chiroptical techniques. The direct antifungal activity of 1 against C. glabrata (MIC = 20 渭M) was higher than that of fluconazole. Sedonans A鈥揊 and ent-sandwicensin were also active against Saccharomyces cerevisiae strains that express differing ABC transporter-associated resistance mechanisms but differed in their susceptibility to Cdr1p-mediated detoxification. A sedonan A (1)/ent-sandwicensin (8) combination exhibited synergistic growth inhibition. The results demonstrate that multiple crude extract compounds are differentially affected by efflux-mediated resistance and are collectively responsible for the observed bioactivity.