Characterization of the effects of new antifungal drug candidates against Candida albicans biofilms

Candida spp. are commonly found among the microbiota of humans and are an increasing health threat to immunocompromised individuals. Candida albicans is the most common causative agent of candidiasis and these infections are commonly associated with the formation of biofilms on both biological surfaces and implanted medical devices. Biofilms are structured microbial communities attached to surfaces and encapsulated within a protective extracellular matrix. Previous studies in our laboratory identified four compounds from the Chembridge Corporation's NOVAcoreTM and DIVERSetTM chemical libraries as initial "hits" against biofilm formation. Here we have screened a total of 72 analogs of these antifungal leads (60 from the NOVAcoreTM library and 12 from the DIVERSetTM library) for their ability to inhibit C. albicans biofilm formation using a 96-well microtiter plate biofilm model. Results indicate that four "lead" compounds (NOVAcoreTM compounds NCA and NCB; DIVERSetTM compounds DS1 and DS2) were the most effective inhibitors of biofilm formation. Follow-up characterization using light microscopy, scanning electron microscopy and confocal scanning laser microscopy has provided additional insight into the biofilm-inhibitory activity and mechanism of action for each of these "lead" compounds. This information will be valuable for the design of more potent and selective antifungal agents against C. albicans biofilms, which are urgently needed.