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