Novel amide derivatives containing an 1,2,4‐oxadiazole moiety as potential SDH inhibitors: design, synthesis, and nematicidal activity

Abstract BACKGROUND The pine wilt disease (PWD) caused by Bursaphelenchus xylophilus is considered the ‘cancer’ of pine trees, and protecting pine forests from the destructive impact of the nematode remains a significant challenge. Chemical control is one of the most effective methods for managing plant nematodes. Developing new nematicides is an effective strategy and an urgent need for Bursaphelenchus xylophilus management. RESULTS Amide derivatives containing 1,2,4‐oxadiazole were designed and synthesized through a scaffold‐hopping strategy. Some target compounds exhibited significant nematicidal activities. For example, compound F3 showed a half‐maximal lethal concentration (LC 50 ) value of 3.63 mg/L against Bursaphelenchus xylophilus . Compound F3 not only significantly inhibited the hatching of eggs, but also reduced the feeding, reproduction, and motility of Bursaphelenchus xylophilus . Additionally, compound F3 induced the accumulation of lipofuscin, lipids, and reactive oxygen species (ROS) in Bursaphelenchus xylophilus , leading to harmful oxidative stress responses. Compound F3 caused severe damage to the intestinal barrier, led to the shrinkage of the nematode surface. Interestingly, compound F3 exhibited a favorable interaction pattern with succinate dehydrogenase (SDH) and was similar to the interaction pattern of fluopyram with SDH. Compound F3 may inhibit the activity of nematode SDH, leading to blockage of electron transfer in the respiratory chain, thereby resulting in nematode death. CONCLUSION Compound F3 can serve as a potential lead compound for SDH inhibitor, with further molecular structure optimization to discover new nematicides in the future. © 2025 Society of Chemical Industry.