Design, Synthesis, and Biological Activity Evaluation of Eco-Friendly Rosin-Diamide-Based Fungicides as Potential Succinate Dehydrogenase Inhibitors for Sustainable Crop Protection

To develop novel succinate dehydrogenase (SDH) inhibitors for sustainable crop protection, a series of dehydroabietyl-diamide-based fungicides (a total of 21) were designed. In vitro fungicidal activity measurement showed that compound 3u exhibited excellent fungicidal activity against Valsa mali (half-maximal effective concentration, EC50 = 0.195 mu g/mL), surpassing that of the positive control carbendazim (EC50 = 1.35 mu g/mL). The in vivo fungicidal activity assessment suggested that 3u exhibited a protective effect on apple branches (69.7-48.1%) and apples (94.6-56.6%). Furthermore, biosafety evaluation indicated that 3u was significantly environmentally friendly toward zebrafish. Subsequently, morphology, physiology, and molecular docking were investigated to elucidate the mode of action of 3u against V. mali. Results demonstrated a strong binding between 3u and SDH, resulting in decreased SDH activity (half-maximal inhibitory concentration, IC50 = 11.7 mu g/mL). Moreover, 3u disrupted the mycelial cell membrane and accelerated electrolyte leakage, ultimately resulting in the death of V. mali. These findings suggest that 3u could serve as a potent SDH inhibitor for sustainable crop protection.