Novel Trifluoromethyl-Substituted Dipyrimidinamine Derivatives as Potential Antifungal Agents for Controlling Postharvest Soft Rot in Kiwifruit

Abstract

Postharvest soft rot poses a severe threat to the kiwifruit industry. In response to this challenge, 20 trifluoromethyl-substituted dipyrimidinamine derivatives were designed and synthesized based on the molecular hybridization strategy. The bioassay results showed that most of the target compounds exhibited good inhibitory activity against plant pathogenic fungi. Among these compounds, compound 6p demonstrated the most potent activity against the postharvest pathogens Botryosphaeria dothidea and Phomopsis sp., with EC50 values of 8.92 and 13.11 μg/mL, respectively, which were significantly better than the commercial fungicide pyrimethanil. At 200 μg/mL, the protective activity and therapeutic activity of compound 6p on kiwifruit were better than the commercial control pyrimethanil. Mechanistic evidence suggested that compound 6p markedly perturbs the structural integrity of the pathogenic fungal membrane, thereby triggering extensive leakage of proteins, nucleic acids, and other cytoplasmic contents, and provoking reactive oxygen species (ROS) accumulation. Molecular docking simulation results indicated strong binding affinity of the compound toward the crystal structure of a homologous cystathionine gamma-synthase. The results of this study provide an important scientific basis and molecular design reference for new trifluoromethylpyrimidine fungicides.