Characterization of Aurone X as a Potential Drug Candidate Against Cryptococcus neoformans

Abstract

Cryptococcus neoformans (Cn) is an opportunistic, fungal pathogen that can spread from the lungs to the central nervous system and cause life-threatening meningitis, most commonly in immune depressed individuals. There are currently four drugs on the market that are the standard treatment; however, these have resulted in renal toxicity, liver failure, and resistant strains. The lack of safe, effective medication for treating cryptococcal meningitis is the motivation for identifying if aurone X is a potential drug candidate by characterizing the compound’s inhibition. The screening of an aurone library using the A27-M2 CLSI standard micro-dilution method identified aurone X, which showed > 90% inhibition to Cn. Toxicity assays conducted on rat L6 fibroblasts and human THP1 macrophages showed minimal toxicity. Additional tests were performed to determine aurone x’s potential as a drug candidate. We characterized the minimum inhibitory concentrations (MIC) of aurone X in different medias, at different cell concentrations, with different serotypes and strains, and tested for synergy with Fluconazole, Flucytosine, and Amphotericin B. Based on our data of aurone X’s low toxicity and effectiveness at low dosages, aurone X could be a possible drug candidate against Cn infections.