Discovery of juglone derivatives as potential nematicides by exacerbating oxidative damage

Plant-parasitic nematodes impose a severe risk to crops, affecting their yield and quality. To discover new nematicides, a series of natural juglone derivatives containing amide fragments, sulfonyl or ester groups were designed and synthesized with the activity-oriented strategy. Bioassays showed that most compounds exhibit good nematicidal activity against Bursaphelenchus xylophilus, Aphelenchoides besseyi, and Ditylenchus destructor. Especially, compound 4r exhibited outstanding nematicidal activity against B. xylophilus with an LC₅₀ value of 9.4 ± 0.3 μg/mL at 48 h, outperforming juglone (LC₅₀ = 15.7 ± 0.3 μg/mL) and fosthiazate (LC₅₀ > 400 μg/mL). The preliminary results of the mechanism study revealed that compound 4r can not only disrupt structure but also affect the behavior, feeding, reproduction, and eggs hatching of B. xylophilus. Especially, compound 4r can promote the production of reactive oxygen species and lipofuscin and lipids within nematodes, leading to elevated malondialdehyde levels and reduced activity of antioxidant enzymes like superoxide dismutase, glutathione-S-transferase, and catalase, thereby exacerbating oxidative damage in nematodes. These findings indicate that natural juglone skeleton is a valuable template for discovering new nematicides, with compound 4r being a promising nematicides candidate.