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Bioorg Med Chem Lett DOI:10.1016/j.bmcl.2011.06.105

Piperazinyl quinolines as chemosensitizers to increase fluconazole susceptibility of Candida albicans clinical isolates.

Publication TypeJournal Article
Year of Publication2011
AuthorsYoungsaye, W, Vincent, B, Hartland, CL, Morgan, BJ, Buhrlage, SJ, Johnston, S, Bittker, JA, MacPherson, L, Dandapani, S, Palmer, M, Whitesell, L, Lindquist, S, Schreiber, SL, Munoz, B
JournalBioorg Med Chem Lett
Date Published2011 Sep 15
KeywordsAntifungal Agents, Calcineurin, Calcineurin Inhibitors, Candida albicans, Dose-Response Relationship, Drug, Fluconazole, HSP90 Heat-Shock Proteins, Microbial Sensitivity Tests, Molecular Structure, Quinolines, Small Molecule Libraries, Stereoisomerism, Structure-Activity Relationship

The effectiveness of the potent antifungal drug fluconazole is being compromised by the rise of drug-resistant fungal pathogens. While inhibition of Hsp90 or calcineurin can reverse drug resistance in Candida, such inhibitors also impair the homologous human host protein and fungal-selective chemosensitizers remain rare. The MLPCN library was screened to identify compounds that selectively reverse fluconazole resistance in a Candida albicans clinical isolate, while having no antifungal activity when administered as a single agent. A piperazinyl quinoline was identified as a new small-molecule probe (ML189) satisfying these criteria.


Alternate JournalBioorg. Med. Chem. Lett.
PubMed ID21802942
PubMed Central IDPMC3287054
Grant ListR03 MH086456-01 / MH / NIMH NIH HHS / United States
10 R03 MH086456-01 / MH / NIMH NIH HHS / United States
U54 HG005032 / HG / NHGRI NIH HHS / United States
1 U54 HG005032-1 / HG / NHGRI NIH HHS / United States
R03 MH086456 / MH / NIMH NIH HHS / United States