Design and Synthesis of Antifungal Candidates Containing Triazole Scaffold from Natural Rosin against Valsa mali for Crop Protection

Two series of dehydroabietyl-1,2,4-triazole-4-Schiff-basedderivativeswere synthesized from rosin to control plant fungal diseases. In vitro evaluation and screening of the antifungal activitywere performed using Valsa mali, Colletotrichum orbiculare, Fusariumgraminearum, Sclerotinia sclerotiorum, and Gaeumannomyces graminis. Compound 3f showed excellent fungicidal activity against V. mali (EC50 = 0.537 mu g/mL), whichwas significantly more effective than the positive control fluconazole(EC50 = 4.707 mu g/mL). Compound 3f alsohad a considerable protective effect against V. mali (61.57%-92.16%), which was slightly lower than that of fluconazole(85.17-100%) at 25-100 mu g/mL. Through physiologicaland biochemical analyses, the preliminary mode of action of compound 3f against V. mali was explored.Ultrastructural observation of mycelia showed that compound 3f hindered the growth of the mycelium and destroyed the ultrastructureof V. mali seriously. Conductivityanalysis and laser scanning confocal microscope staining showed thatcompound 3f changed cell-membrane permeability and causedaccumulation of reactive oxygen species. The enzyme activity resultsshowed that compound 3f significantly inhibited the activityof CYP51 (59.70%), SOD (76.9%), and CAT (67.86%). Molecular dockingidentified strong interaction energy between compound 3f and crystal structures of CYP51 (-11.18 kcal/mol), SOD (-9.25kcal/mol), and CAT (-8.79 kcal/mol). These results provideguidance for the discovery of natural product-based antifungal pesticidecandidates.