ML212: A small-molecule probe for investigating fluconazole resistance mechanisms in Candida albicans

Beilstein Journal of Organic Chemistry

Barbara J. Morgan¹  Amal Ting¹  Partha P. Nag¹  Willmen Youngsaye¹  Stuart L. Schreiber¹  Sivaraman Dandapani¹  Michelle Palmer¹  Joshua A. Bittker¹  Carrie A. Mosher¹  Benito Munoz¹  Cathy L. Hartland¹  Benjamin Vincent²  Luke Whitesell²  Susan Lindquist² 

[1] Chemical Biology Platform and Probe Development Center, Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA;Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA;

关键词: antifungal;    Candida albicans;    chemosensitizer;    fluconazole;    Molecular Libraries Probe Production Center Network (MLPCN);   

DOI  :  10.3762/bjoc.9.171

来源: DOAJ

【 摘 要 】

The National Institutes of Health Molecular Libraries and Probe Production Centers Network (NIH-MLPCN) screened >300,000 compounds to evaluate their ability to restore fluconazole susceptibility in resistant Candida albicans isolates. Additional counter screens were incorporated to remove substances inherently toxic to either mammalian or fungal cells. A substituted indazole possessing the desired bioactivity profile was selected for further development, and initial investigation of structure–activity relationships led to the discovery of ML212.

【 授权许可】

Unknown