Design, Synthesis, and Nematicidal Activity of Novel Amide Derivatives Containing an 1,2,4/1,3,4-Oxadiazole Moiety against .

To discover novel structural nematicides, 79 amide compounds containing 1,2,4/1,3,4-oxadiazole moiety were designed, synthesized, and evaluated for nematicidal efficacy against second-stage juveniles of (). Notably, some compounds exhibited superior nematicidal efficacy, for example, the LC values of compounds , , , , , , , and were 7.4, 31.0, 35.3, 10.3, 12.7, 6.9, 21.5, and 52.2 mg/L, respectively, with nematicidal activities significantly surpassing that of tioxazafen (79.3 mg/L). Compound exhibited multifaceted nematicidal activity through suppression of motility, feeding, and reproduction, combined with induction of oxidative stress. Compound significantly reduced nematode protein content and impaired antioxidant capacity. Meanwhile, compound demonstrates superior binding energy and interaction mode with succinate dehydrogenase (SDH), showing potent SDH inhibition (IC = 15.0 μmol/L). Therefore, compound , which may become a potential SDH inhibitor, interferes with nematode energy metabolism by inhibiting SDH activity, resulting in nematode death.