Design, synthesis, antifungal evaluation and mechanism study of myrtenal derivatives as potential laccase inhibitors

Abstract BACKGROUND To develop novel natural product‐derived fungicides, four series of myrtenal oxadiazole/thiadiazole‐hydrazide/amide derivatives were designed, synthesized and evaluated for their inhibitions toward several crop pathogenic fungi/oomycetes. RESULTS In the in vitro antifungal experiments, some myrtenal derivatives showed good antifungal activity against Botryosphaeria dothidea, Sclerotinia sclerotiorum and Fusarium graminearum . Among them, compound 6d exhibited the best antifungal activity against B. dothidea , with EC 50 value of 0.052 mg/L, which was significantly stronger than carbendazim (EC 50 = 0.40 mg/L). In vivo antifungal activity assay on apple fruits and branches showed that 6d displayed significant protective and curative effects, both superior to carbendazim. In the preliminary antifungal mechanism study, 6d can damage the surface morphology of mycelia, destroy the integrity and permeability of cell membrane, increase intracellular ROS content, thereby inhibiting the growth of B. dothidea . Compound 6d also significantly inhibited laccase with IC 50 value of 8.45 μM, much stronger than cysteine and PMDD‐5Y. Molecular docking also confirmed the binding affinity and interaction mode of 6d with laccase. CONCLUSION This study presented a promising lead compound for the study on novel laccase inhibitors as fungicidal agrochemicals, which demonstrated significant anti‐ B. dothidea activity and laccase inhibitory activity. © 2025 Society of Chemical Industry.