Synthesis and evaluation of antifungal peptoid derivatives against Cryptococcus neoformans

Abstract

The fungi Cryptococcus neoformans is often the cause of cryptococcal meningitis in immunocompromised individuals. High focus has been placed on searching for antimicrobial drugs that have a relatively long half-life in vivo while also retaining a low mammalian cytotoxicity. The purpose of this project is to synthesize repeat and multimeric derivatives of a known antifungal peptoid, termed β-5, in an effort to increase the potency against the fungi Cryptococcus neoformans without increasing cytotoxicity towards mammalian cells. Repeats and multimeric derivatives of β-5 have successfully been synthesized, following protocols previously reported from our lab. These derivatives have been evaluated by traditional minimum inhibitory concentration (MIC) assays to evaluate antifungal potency. These derivatives have also been tested against HepG2 hepatocytes and erythrocytes to evaluate mammalian cytotoxicity. The future plans for this project are to begin synthesizing cyclic derivatives of β-5.