Discovery and optimization of a small molecule series that induces a novel isotropic growth phenotype in C. Albicans

MEDI 409

Scott Collibee1, Thomas Lila2, Bradley Morgan1, Penelope Chua3, Matthew Hamilton1, Takashi Nakai1, Daniel Pierce2, David J. Morgans Jr.4, Charles Vacin2, and David Clarke5. (1) Department of Medicinal Chemistry, Cytokinetics, Inc, 280 East Grand Ave, South San Francisco, CA 94080, (2) Assay Development, Cytokinetics, Inc, 280 East Grand Ave, South San Francisco, CA 94080, (3) Department of Cancer Biology and Therepeutics, Cytokinetics, Inc, 280 East Grand Ave, South San Francisco, CA 94080, (4) Cytokinetics, Inc, 280 E Grand Ave., South San Francisco, CA 94080, (5) Cell Technologies, Cytokinetics, Inc, 280 East Grand Ave, South San Francisco, CA 94080
Yeast cells can respond to perturbation of the cell cycle or cytoskeleton with distinctive changes in extracellular and nuclear morphologies. An automated fluorescence-microscopic screen of 6800 known C. albicans pump mutant growth inhibitors was performed to identify small molecules that alter the morphology of Candida albicans. Compounds that caused diverse morphological phenotypes were identified, including one that induced an isotropic growth phenotype similar to that observed for a C. albicans cdc42 mutation strain. Optimization revealed members with broad activity against pathogenic yeast species (C. albicans, C. glabrata, and C. tropicalis) and low human cell toxicity.
 

Poster Session
7:00 PM-9:00 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster

Sci-Mix
8:00 PM-10:00 PM, Monday, August 20, 2007 BCEC -- Exhibit Hall - B2, Sci-Mix

Division of Medicinal Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007