Synthesis and Characterization of Cyclic Peptoids Against Cryptococcus neoformans and Candida albicans

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Sibley, Ross
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University Honors College, Middle Tennessee State University
Antimicrobial resistant strains of fungal pathogens such as Cryptococcus neoformans and Candida albicans have risen to concerning heights, necessitating the discovery of a safe and effective novel antimicrobial agent. Peptoids, N-substituted peptide mimics, are one class of compounds with increasing interest due to improved stability and bioavailability compared to their peptide counterparts. RMG8-8 and RMG9-11 are two peptoids recently discovered in the Bicker Lab with observed antifungal activity against Cryptococcus neoformans and Candida albicans, respectively. This study attempted to optimize antifungal activity of RMG8-8 and RMG9-11 through cyclization. Following synthesis, cyclic RMG8-8 (RHS3) and cyclic RMG9-11 (RHS6) were characterized by minimum inhibitory concentration (MIC90) against the two fungal pathogens, mammalian cytotoxicity (MTT) against HepG2 liver cells, and hemolytic activity against human red blood cells. Despite neither of the cyclic peptoids significantly outperforming their linear parent compound, future optimization efforts may be investigated.