A yeast-killing compound evades drug resistance and is less toxic than a related drug used in the clinic.

The antifungal drug amphotericin B (AmB) does not typically result in resistant fungi, but it kills human cells so can be used only at low doses. To create AmB derivatives that are less toxic to humans and do not cause resistance, Susan Lindquist at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, Martin Burke at the University of Illinois at Urbana-Champaign and their colleagues used just three steps of chemical synthesis.

The new compounds killed infectious yeast in the lab and in mice, but were less toxic to human cells and mice than AmB. Yeast strains that were resistant to the compounds in vitro were unable to cause lethal infections in mice, unlike non-resistant strains, suggesting that drug-resistant strains are less fit.

The new antifungals kill yeast by pulling out ergosterol molecules from the yeast cell wall, but they do not bind to the similar molecule cholesterol in animal cell membranes.

Nature Chem. Biol. http://dx.doi.org/10.1038/nchembio.1821 (2015)