Identification and structure-activity relationship studies of clavatol as an antifungal compound against pathogenic plant fungi using a drug-hypersensitive fission yeast screening system.

Our original drug-hypersensitive fission yeast-based fungicide screening system identified clavatol (1) as a selective active compound against drug-hypersensitive fission yeast (more than 30-fold selectivity over multidrug-sensitive budding yeast). Compound 1, which was originally isolated from Penicillium species, has several biological activities including a very weak antifungal activity against Botrytis cinerea (the 50% effective concentration (EC50) value was 0.058 mg/mL). However, the selectivity of 1 against drug-hypersensitive fission yeast over the budding yeast prompted us to investigate overlooked antifungal activities. After evaluation, we revealed that 1 showed great antifungal activity against quinone outside inhibitors (QoI)-resistant Pyricularia oryzae. Furthermore, we evaluated the anti-P. oryzae activity of 8 compounds having structural features similar to those of 1 in order to elucidate the structure-activity relationship. Our research indicates that the drug-hypersensitive fission yeast-based fungicide screening system is a useful approach for discovering new fungicidal candidates and that 1 has great potential and would be a promising natural product as an agrochemical seed.