Antifungal Activity of Brilacidin, a Nonpeptide Host Defense Molecule

Natural host defensins, also sometimes termed antimicrobial peptides, are evolutionarily conserved. They have been studied as antimicrobials, but some pharmaceutical properties, undesirable for clinical use, have led to the development of synthetic molecules with constructed peptide arrangements and/or peptides not found in nature. The leading development currently is synthetic small-molecule nonpeptide mimetics, whose physical properties capture the characteristics of the natural molecules and share their biological attributes. We studied brilacidin, an arylamide of this type, for its activity in vitro against fungi (40 clinical isolates, 20 species) that the World Health Organization has highlighted as problem human pathogens. We found antifungal activity at low concentrations for many pathogens, which indicates that further screening for activity, particularly in vivo, is justified to evaluate this compound, and other mimetics, as attractive leads for the development of effective antifungal agents.