Optimization of Luteoride A Derivatives as Potential Broad-Spectrum Fungicide Agents for Plant Protection

Natural products remain an important source of highly effective, low-risk pesticides. In this study, a series of luteoride A derivatives were designed and synthesized through diversified modification; their fungicidal activities were evaluated against six prevalent plant pathogenic fungi. In vitro antifungal assays revealed that compound C5 exhibited the highest potency against Valsa mali with an EC₅₀ of 0.771 mg/L. Compound D4 displayed broad-spectrum inhibitory activities against V. mali, Botrytis cinerea, and Physalospora piricola with EC₅₀ values of 2.17, 0.479, and 4.84 mg/L, respectively. In vivo assays demonstrated that compound D4 effectively controlled B. cinerea infection on tomatoes at a concentration of 100 mg/L, outperforming the positive control trifloxystrobin. The in vitro enzymatic inhibition experiments and molecular docking analysis suggested that compound D4 may interfere with respiratory metabolism by binding to complex III. This study lays the foundation for developing luteoride A derivatives as promising candidate fungicides for crop protection.