Discovery of febrifugine with specific anti-Phytophthora oomycete activity isolated from Dichroa febrifuga Lour

Dichroa febrifuga has been used in traditional Chinese medicine for centuries to treat productive cough and fevers caused by malaria infection, however the antimicrobial activity is still unknown. In this study, the crude alkaloids extract of D. febrifuga leaves showed potent anti-oomycete activity against phytopathogen Phytophthora capsici. Subsequent bioassay-guided fractionation led to identify febrifugine as the main active component. Febrifugine showed specific in vitro anti-oomycete activity against P. capsici, Phytophthora sojae and Phytophthora infestans with EC50 of 1.741, 1.674 and 0.413 μg/mL, respectively, but showed no or weak antifungal activity against twelve test phytopathogenic fungi. Scanning electron microscope and optical microscope results indicated that febrifugine could alter the morphology of P. infestans hyphae, but did not destroy the cell wall. The electrical conductivity and intracellular component leakage experiments suggested the integrity of the cell membrane after the treatment of febrifugine. Moreover, febrifugine possessed inhibitory effects on zoospore release and germination of P. infestans. In vivo bioassay using detached leaves demonstrated that febrifugine had better protective and curing activities than commercialized drug metalaxyl. The application of febrifugine at a dose of 60 μg/mL provided protective efficacies of 93.1% and 91.9%, and curing efficacies of 86.2% and 86.6% for pepper phytophthora blight and potato late blight, respectively. Taken together, this study showed that the crude alkaloids extract of D. febrifuga and its active component febrifugine represent alternatives to control plant diseases caused by oomycetes, and febrifugine is expected to be a new leading structure for the development of oomyceticides.