Device-related infections (DRIs) from bacterial/fungal biofilms that form on surfaces are a major cause of death in first-world countries. DRIs and the increasing prevalence of antibiotic resistant strains require development of new antimicrobials for improved antimicrobial prophylaxis. New antimicrobial prophylaxis practices necessitate novel agents to combat a broad spectrum of both fungi and bacteria, to be less toxic to patients, and to be locally administrable to prevent perturbations to patient’s microbiome. A class of antimicrobials that we have previously developed to fit these criteria is ceragenins. Here we describe the design, synthesis, and characterization of a new series of ceragenins that is composed of and degrades into endogenous compounds: cholic acid, B alanine, and glycerides. From this series we identify an optimized bioresorbable ceragenin that has comparable antimicrobial activities to other ceragenins, degrades rapidly through the action of lipase and at pH 7.2, and has a similar mechanism of action to previously developed ceragenins.
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