Publication Type | Journal Article |
Year of Publication | 2011 |
Authors | Youngsaye, 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 |
Journal | Bioorg Med Chem Lett |
Volume | 21 |
Issue | 18 |
Pages | 5502-5 |
Date Published | 2011 Sep 15 |
ISSN | 1464-3405 |
Keywords | Antifungal 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 |
Abstract | 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. |
DOI | 10.1016/j.bmcl.2011.06.105 |
Pubmed | |
Alternate Journal | Bioorg. Med. Chem. Lett. |
PubMed ID | 21802942 |
PubMed Central ID | PMC3287054 |
Grant List | R03 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 |