Agrochemical Lessons for Infectious Disease Research: New Resistance Breaking Antifungal Hits against Candida auris

Analysis of the history of the invention of the block-buster antifungal drug Fluconazole underscores the importance of agrochemical research on drug discovery and development. The multidrug resistant fungal pathogen Candida auris is now responsible for serious morbidity and mortality among immuno-compromised and long-term resident hospital patients globally. New drugs against C. auris are urgently needed. A focused screening of 1487 fungicides from the BASF agrochemical collection gave several potent inhibitors of C. auris with yet noncommercialized modes of action. The hits showed only minor activity loss against the azole-resistant C. auris strain CDC 0385 and low to moderate cytotoxicity to human HepG2 cells. Aminopyrimidine 4 showed high activity against resistant strains and selectivity in a HepG2 cells assay and is a potential hit candidate for further optimization.