The infection and resistance of pathogenic fungi pose a significant threat to food crop safety, highlighting the urgent need for new green antifungal agents. Fusarium acid (FA) with its simple and novel structure correlates with the principles of green pesticides and has demonstrated substantial broad-spectrum antifungal activity. In a previous study, several promising lead compounds were identified. This study focused on further optimizing lead compound A1. Its inhibitory effect was evaluated against six different pathogenic fungi and several new promising compounds were identified. Notably, the anti-Magnaporthe oryzae (M. oryzae) activity of compound B4 was significantly enhanced with an EC50 value of 910 ng/mL. Rice safety tests indicated that B4 not only exhibited no adverse effect on rice growth and chlorophyll synthesis but also induced plant immunity by increasing the levels of polyphenol oxidase (PPO), peroxidase (POD), and superoxide dismutase (SOD), and soluble sugars. Further investigations into the antifungal mechanism of B4 indicated that it enhanced the permeability and damage of the mycelial membrane, thereby leading to electrolyte leakage and the loss of essential cellular substances. Subsequently, B4 induced the production of reactive oxygen species (ROS) in M. oryzae cell, including •OH, •O2-, and 1O2, while promoting increased levels of malondialdehyde (MDA) and SOD enzyme activity. Rice infection tests indicated that B4 effectively inhibited M. oryzae conidia activity and inhibited melanin production. These findings indicated that FA derivatives hold significant potential as a new strategy for M. oryzae disease management and offer valuable insights for the control of plant fungal diseases.
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