1,2,4-Oxadiazole-5-Carboxylic Acid Derivatives as Safe Seed Treatment Nematicides

Plant-parasitic nematodes pose a significant threat to crop production, impacting agricultural yields. In the search for new nematicides, a series of 1,2,4-oxadiazole-5-carboxylic acid derivatives containing amide or ester groups were designed and synthesized using an activity-based approach. Bioassay results showed that some compounds exhibited good nematicidal activity against <i>Meloidogyne incognita</i>, <i>Aphelenchoides besseyi</i>, and <i>Bursaphelenchus xylophilus</i>. Especially, compound <b>f1</b> showed excellent nematicidal activity against <i>A. besseyi</i> with an LC₅₀ value of 19.0 μg/mL at 48 h, outperforming tioxazafen (LC₅₀ = 149 μg/mL) and fosthiazate (LC₅₀ > 300 μg/mL). In semi-<i>in vivo</i> and pot experiments, compound <b>f1</b> demonstrated superior nematicidal activity compared to fosthiazate against <i>A. besseyi</i> while also being safe for rice seeds. The mechanism of action revealed that compound <b>f1</b> could inhibit the population and behavior of <i>A. besseyi</i>, damage the nematode cuticle, resulting in fluid leakage, affect the production of reactive oxygen species, lipofuscin, and lipids in nematodes, and inhibit acetylcholinesterase in <i>A. besseyi</i>. These findings suggest that compound <b>f1</b> has the potential to be a safe and effective seed treatment nematicide.