Quinofumelin and Other Dihydroorotate Dehydrogenase Inhibitors

Quinofumelin, a novel fungicide developed by Mitsui Chemicals Crop and Life Solutions, Inc., has a novel chemical structure that includes 3-(isoquinolin-1-yl)quinoline. This structure allows it to exhibit fungicidal activity against a wide range of fungi, including strains resistant to existing treatments. The target site of quinofumelin has been identified as class 2 dihydroorotate dehydrogenase (DHODH), an enzyme that catalyzes the oxidation of DHO to orotate. Remarkably, quinofumelin shows a higher degree of selectivity for fungal DHODH than its human counterpart. A comparison of the amino acid sequences of human and fungal DHODHs reveals a significant difference at the ubiquinone-binding site. This difference is believed to contribute to the species selectivity of quinofumelin, making it a promising tool in the fight against fungal diseases.