Screening of Compounds from an FDA-Approved Drug Library for the Ability to Inhibit Aspartic Protease Secretion from the Pathogenic Yeast Candida albicans

Abstract

The pathogenic fungus Candida albicans causes disseminated candidiasis with a poor prognosis in immunocompromised hosts. Secreted aspartyl protease (Sap) from the microorganism acts as a hydrolase to facilitate invasion into host tissues. Inhibition of Candida Sap activity could be a new treatment strategy for candidiasis. In the present study, we screened compounds from an FDA-approved drug library, Screen-Well, for their ability to inhibit Candida Sap activity. Sixteen compounds (piroxicam, carbidopa, nisoldipine, cerivastatin, fluvastatin, mycophenolic acid, rapamycin, bleomycin, bortezomib, 5-fluorouracil, floxuridine, fumagillin, pentamidine, albendazole, fenbendazole, and amprenavir) inhibited Sap activity in a dose-dependent manner in vitro, although strain differences in the activity of the compounds were observed. Our study shows that existing drug compounds have the potential to inhibit Sap activity.