Discovery of Novel Amide Derivatives Containing an Oxazole/Isoxazole Moiety as Potential SDH Inhibitors: Design, Synthesis, and Nematicidal Activity

To develop new nematicides, amide derivatives with oxazole/isoxazole were synthesized via scaffold-hopping as succinate dehydrogenase (SDH) inhibitors. The nematicidal activities of these target compounds were tested against Bursaphelenchus xylophilus, Aphelenchoides besseyi, and Ditylenchus destructor. Some of the compounds showed excellent nematicidal activities. Compound B21 had LC₅₀ values of 3.2 mg/L for B. xylophilus, 11.5 mg/L for A. besseyi, and 10.5 mg/L for D. destructor. Compound B21 exerted a pronounced inhibitory effect on feeding, reproduction, and embryonic development capabilities of B. xylophilus, while concurrently triggering deleterious oxidative stress responses within the nematodes. These reactions led to intestinal damage and eventually death of the nematodes. Compound B21 exhibited strong hydrophobic interactions with the residues Arg-76, Val-103, Pro-193, and Ile-242 of SDH. Additionally, B21 significantly inhibited the SDH of B. xylophilus, with an IC₅₀ value of 6.5 μmol/L.