|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||Bioorganic & medicinal chemistry letters|
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.