Reversal of Fluconazole Resistance by Sulfated Sterols from the Marine Sponge Topsentia sp.

被引：44
|
作者：
DiGirolamo, Jessica A. [1 ]
Li, Xing-Cong [1 ,2 ]
Jacob, Melissa R. [2 ]
Clark, Alice M. [1 ,2 ]
Ferreira, Daneel [1 ,2 ]
机构：
[1] Univ Mississippi, Sch Pharm, Dept Pharmacognosy, University, MS 38677 USA
[2] Univ Mississippi, Sch Pharm, Natl Ctr Nat Prod Res, University, MS 38677 USA
来源：
JOURNAL OF NATURAL PRODUCTS | 2009年 / 72卷 / 08期
关键词：
ANTIFUNGAL DRUG-RESISTANCE; CANDIDA-ALBICANS; CONFERRING RESISTANCE; TRANSPORTER GENE; MECHANISMS; INHIBITORS; AGENTS; FUNGI; AIDS;
D O I：
10.1021/np900177m
中图分类号：
Q94 [植物学];
学科分类号：
071001 ;
摘要：
Bioassay-guided fractionation of the extract of Topsentia sp. led to the identification of two new sulfated sterols, geodisterol-3-O-sulfite (1) and 29-demethylgeodisterol-3-O-sulfite (2), the active constituents reversing efflux pump-mediated fluconazole resistance. Both compounds enhanced the activity of fluconazole in a Saccharomyces cerevisiae strain overexpressing the Candida albicans efflux pump MDR1, as well as in a fluconazole-resistant Candida albicans clinical isolate known to overexpress MDR1. These results provide insight into the clinical utility of combining efflux pump inhibitors with current antifungals to combat the resistance associated with opportunistic fungal infections caused by C. albicans.
引用
收藏
页码：1524 / 1528
页数：5
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