Discovery of double 1,2,4‐oxadiazole derivatives as promising nematicides

Abstract BACKGROUND Plant parasitic nematodes severely impair agricultural and forestry production due to the lack of effective nematicides, causing significant yield losses and economic damage. RESULTS For discovery of new and efficient nematicidal agents, we developed a series of double 1,2,4‐oxadiazole derivatives from our previous studies. Bioassays revealed that compounds B10 and B12 displayed 100% mortality against Bursaphelenchus xylophilus , Aphelenchoides besseyi and Ditylenchus destructor at 50 μg mL −1 . In particular, compound B10 was the most potent against B . xylophilus , showing a median lethal concentration (LC 50 ) of 5.85 μg mL −1 , which outperformed the lead compound tioxazafen (LC 50 = 180.02 μg mL −1 ) by a clear margin. Preliminary mechanistic investigations indicated that B10 significantly suppressed the feeding and reproductive capacity of B. xylophilus, and induced substantial accumulation of intracellular reactive oxygen species, lipofuscin and lipids, accompanied by elevating malondialdehyde levels and suppressed activities of antioxidant‐related enzymes, and then triggerred oxidative damage by disrupting redox homeostasis. Transcriptome analysis indicated that B10 strongly affected gene expression, with most the differentially expressed genes mainly associated with the neuroactive ligand–receptor interaction pathway. These results were further supported by quantitative reverse‐transcription PCR analysis and acetylcholinesterase activity assays. CONCLUSION The present work indicated that double 1,2,4‐oxadiazole compound B10 is a promising nematicide for managing nematode diseases. © 2026 Society of Chemical Industry.