DIHYDROOROTATE DEHYDROGENASE AS ANTIFUNGAL DRUG TARGET AND QUINAZOLINONE-BASED INHIBITORS THEREOF

摘要

Disclosed is a method of identifying an antifungal agent which targets a dihydroorotate dehydrogenase (DHODH) protein of a fungus comprising contacting a candidate substance with a fungal DHODH protein and determining whether the candidate substance inhibits the DHODH protein, wherein inhibition indicates that the candidate substance is an antifungal agent and wherein inhibition of the DHODH protein is measured by the addition of: (a) a quinone selected from ubiquinone 5 (coenzyme Q1) and ubiquinone 10 (coenzyme Q2) and (b) an electron acceptor and detecting the reduction of the electron acceptor.