Dual membrane- and DNA-targeting antifungal for drug-resistant pathogens

A synthetic naphthalene-poly(2-oxazoline) could help treat drug-resistant fungal infections by targeting the membrane and DNA of the pathogen simultaneously, with greater selectivity for fungal cells than marketed membrane-targeting compounds.

Structure-guided optimization of a series of poly(2-oxazoline)s, which mimic membrane-disrupting antimicrobial peptides, that contained varying amounts of DNA-binding naphthalene residues, yielded a series of compounds. In primary human red blood cells, the compounds induced hemolysis with IC50s of 1,000–2,000 µg/mL, while the marketed antifungal amphotericin B, which binds ergosterol and forms pores in fungal cell membranes, induced hemolysis with an IC50 of 3 µg/mL. ...