Overcoming fluconazole resistance in Candida albicans clinical isolates with tetracyclic indoles

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:22

Article

Youngsaye, Willmen¹  Dockendorff, Chris¹  Vincent, Benjamin^2,3  Hartland, Cathy L.¹  Bittker, Joshua A.¹  Dandapani, Sivaraman¹  Palmer, Michelle¹  Whitesell, Luke²  Lindquist, Susan^2,4,5  Schreiber, Stuart L.^1,6  Munoz, Benito¹ 

[1] Broad Inst MIT & Harvard, Chem Biol Platform & Probe Dev Ctr, Cambridge, MA 02142 USA

[2] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA

[3] MIT, Microbiol Grad Program, Cambridge, MA 02139 USA

[4] MIT, Dept Biol, Cambridge, MA 02139 USA

[5] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA

[6] Broad Inst Harvard & MIT, Howard Hughes Med Inst, Cambridge, MA 02142 USA

关键词: Candida albicans;    Fluconazole;    Antifungal;    Chemosensitizer;    Molecular libraries probe production center network (MLPCN);   

DOI  :  10.1016/j.bmcl.2012.02.035

来源: Elsevier

【 摘 要 】

Continuing efforts to discover novel means of combating fluconazole resistance in Candida albicans have identified an indole derivative that sensitizes strains demonstrating resistance to fluconazole. This tetracycle (3, ML229) does not appear to act through established Hsp90 or calcineurin pathways to chemosensitize C. albicans, as determined in Saccharomyces cerevisiae models, and may be a useful probe to uncover alternative resistance pathways. (C) 2012 Elsevier Ltd. All rights reserved.

【 授权许可】

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