Mode of action of novel acaricide pyflubumide: Effects on the mitochondrial respiratory chain

This study aimed to determine the mode of action of pyflubumide, a novel acaricide under development by Nihon Nohyaku Co., Ltd. Because of its structural similarity to succinate-dehydrogenase inhibitor (SDHI) fungicides, its ability to inhibit mitochondrial complex II was investigated. Pyflubumide exhibited low inhibitory activity on spider mite mitochondria; conversely, its deacylated metabolite (NH-form) showed high mitochondrial inhibitory activity. Pyflubumide was quickly metabolized to its NH-form in the homogenate of spider mites. These results suggest that pyflubumide is a prodrug and that the NH-form is active. Indeed, the NH-form of pyflubumide and the OH-form of cyenopyrafen, a complex II inhibitory acaricide, act on the same enzyme; a double-inhibitor titration assay showed that the binding sites on mitochondrial complex II and/or the manners of binding of these compounds exhibit clear differences. This finding suggests that these two acaricides should be classified into different groups in terms of their mode of action.