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

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 Bursaphelenchus xylophilus (B. xylophilus). Notably, some compounds exhibited superior nematicidal efficacy, for example, the LC₅₀ values of compounds 11, 39, 40, 48, 49, 51, 52, and 54 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 51 exhibited multifaceted nematicidal activity through suppression of motility, feeding, and reproduction, combined with induction of oxidative stress. Compound 51 significantly reduced nematode protein content and impaired antioxidant capacity. Meanwhile, compound 51 demonstrates superior binding energy and interaction mode with succinate dehydrogenase (SDH), showing potent SDH inhibition (IC₅₀ = 15.0 μmol/L). Therefore, compound 51, which may become a potential SDH inhibitor, interferes with nematode energy metabolism by inhibiting SDH activity, resulting in nematode death.