4-(Diethylamino)salicylaldehyde exerts nematicidal activity against Ditylenchus destructor via PDH-targeted multi-pathway synergistic mechanism

Plant-parasitic nematodes pose a severe threat to global agricultural production, creating an urgent demand for green and highly efficient nematicides. In this study, we investigated the nematicidal activity and underlying action mechanism of 4-(diethylamino)salicylaldehyde (DSA) against Ditylenchus destructor . DSA exhibited significant nematicidal activity with a 72 h LC₅₀ of 1.951 μg/mL. At 10 μg/mL, DSA completely inhibited nematode infection, comparable to fluopyram. DSA damaged the body wall, induced reactive oxygen species accumulation and lipid peroxidation, and inhibited antioxidant enzymes. Multi-omics analysis revealed that DSA disrupted glycolysis and the TCA cycle, suppressed pyruvate dehydrogenase activity, and reduced ATP levels. Molecular docking and site-directed mutagenesis confirmed that DSA directly targets the PDH E1α subunit via Arg93 and Tyr92. Notably, DSA showed low toxicity to mammals, birds, and silkworm, with only moderate toxicity to zebrafish. Collectively, this study reveals a PDH-targeted, multi-pathway synergistic nematicidal mechanism of DSA, providing a theoretical basis and a promising lead compound for green nematicide development.