Discovery of novel 8-methoxyquinoline oxime derivatives bearing 1,3,4-oxadiazole moieties as potential antifungal agents.

The extensive use of traditional fungicides has led to increasing resistance among phytopathogenic fungi, necessitating the urgent development of novel, highly effective, and green antifungal agents. Here, a series of novel 8-methoxyquinoline oxime derivatives bearing 1,3,4-oxadiazole moieties X1-20 was synthesized through the active substructure splicing strategy. The results of antifungal activity screening indicated that compounds X4 and X7 exhibit broad-spectrum inhibitory activity against four species of phytopathogenic fungi. Notably, compound X7 had an EC50 of 0.089 μmol/mL against Botrytis cinerea, comparable to the positive control Chlorothalonil. Moreover, X7 demonstrated potent in vivo preventive and therapeutic efficacy against B. cinerea, comparable to Chlorothalonil. Mechanistic studies revealed that X7 may interact with β-glucan in the cell wall of B. cinerea, thereby disrupting the normal physiological functions of the cell wall. Additionally, X7 damages the mycelial cell membranes, leading to electrolyte leakage and promoting the release of reactive oxygen species (ROS) to accelerate fungal death. Finally, X7 exhibited lower in vitro and in vivo toxicity than Chlorothalonil, indicating superior biosafety. These findings demonstrate that X7 holds potential for further development as a novel green fungicide.