Synthesis, Fungicidal Activity, and Action Mode Investigations of Novel Nitrophenyl (Z)-3,3-Diaryl Acrylates

Uncoupling agents involved in the oxidative phosphorylation process are a category of bioactive molecules that have garnered significant attention; however, their applications in agriculture remain limited. In this study, we employed a scaffold-hopping strategy to design and synthesize a new class of phenyl acrylates. This was achieved by substituting the methylacryloyl group in dinocap with 3,3-diarylacryloyl derivatives featuring a pyridine ring, which shows affinity for mitochondrial respiratory chain complexes. Through fungicidal activity evaluations, we identified compounds such as Ia-7, Ib-7, and Ic-7 that exhibit significantly greater activity compared to meptyl dinocap. Notably, the EC₅₀ of Ia-7's protective effect against wheat powdery mildew was 3.98 μg/mL, slightly higher than that of fluopyram (3.17 μg/mL) but considerably lower than that of fluazinam (10.04 μg/mL), indicating its potential as a candidate fungicide. Structure-activity relationship analysis revealed that the pK_a value of the phenolic unit is a crucial factor influencing its activity, although it is not the sole determinant. This suggests that it may function as a prodrug, similar to binapacryl, primarily via the release of phenol with uncoupling activity. Other molecular components also contribute to the overall activity, as made evident by the rapid biodegradation of Ib-7. Analyses of biodegradable products, transcriptomic profiles, and ATPase activity indicate that the mechanisms of action of these compounds are intricate, predominantly centered on oxidative phosphorylation. As an uncoupling agent, their mode of action shares both similarities and differences with fluazinam.