Discovery of a new chemical scaffold for the treatment of superbug Candida auris infections.

has emerged as a serious threat of public health and caused global epidemic due to multi-drug resistance, remarkable transmissibility and high mortality. To tackle the challenging super fungus, novel benzoanilide antifungal agents were discovered by an integrated strategy of phenotypic screen, hit optimization, antifungal assays and mechanism exploration. The most promising compound showed potent and efficacy against infection. Mechanism investigation revealed that compound blocked the biosynthesis of virulence factors and fungal cell walls through the inhibition of glycosylphosphatidylinositol (GPI) and GPI-anchored proteins. Thus, compound represents a promising lead compound to combat drug-resistant candidiasis.Novel benzoanilide antifungal agents were discovered to treat multi-resistant infections by an integrated strategy of phenotypic screen, hit optimization, antifungal assays and mechanism exploration. The most promising compound inhibited the biosynthesis of GPIs and GPI-anchored proteins, which showed potent and efficacy against infection.