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

Bioorg Med Chem Lett
Authors
Keywords
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.

Year of Publication
2011
Journal
Bioorg Med Chem Lett
Volume
21
Issue
18
Pages
5502-5
Date Published
2011 Sep 15
ISSN
1464-3405
DOI
10.1016/j.bmcl.2011.06.105
PubMed ID
21802942
PubMed Central ID
PMC3287054
Links
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