Synthesis and Characterization of Antifungal Peptoids against Cryptococcus by Means of Structure Activity Relationship

Abstract

The impending rise in antimicrobial resistance has necessitated alternative therapeutic options for resistant pathogens such as Cryptococcus neoformans. C. neoformans is the causative agent of cryptococcal meningitis, which can be deadly to immunocompromised individuals if it integrates into the central nervous system. Current research has been done with antimicrobial peptide mimics, termed peptoids, as a therapeutic agent for C. neoformans infections. Our primary goal is to optimize the therapeutic potential of the antifungal peptoid AEC5. A sarcosine scan was used to identify the most pharmacophorically important peptoid building blocks of AEC5, followed by sequential optimization of each building block through Structure Activity Relationship studies. We report an optimized antifungal peptoid from this study, β-5, has improved potency towards C. neoformans and decreased toxicity towards mammalian cells. Further studies are focusing on these antifungal peptoids’ mechanism of action in C. neoformans cell death.