Novel Pesticide\nCandidates Inspired by Natural Neolignan:\nPreparation and Insecticidal Investigation of Honokiol Analogs Containing\n2‑Aminobenzoxazole-Fused Core Scaffold

As\na continuation of our efforts to develop new agrochemicals with\ntypical architecture and efficient bioactivity from plant natural\nproducts, natural neolignan honokiol was used as a lead compound to\nprepare novel analogs bearing the core 2-aminobenzoxazole scaffold.\nTheir insecticidal potency against two representative agricultural\npests, Plutella xylostella Linnaeus\nand Mythimna separata (Walker), were\nevaluated in vivo. The pesticide bioassay results revealed that compounds <b>7″a</b>, <b>9</b>, <b>10d</b>, and <b>10j</b> exhibited prominent larvicidal activity against the larvae of P. xylostella (LC<sub>50</sub> = 7.95, 11.85, 15.51,\nand 12.06 μg/mL, respectively), superior to the precursor honokiol\n(LC<sub>50</sub> = 43.35 μg/mL) and two botanical insecticides,\ntoosendanin (LC<sub>50</sub> = 26.20 μg/mL) and rotenone (LC<sub>50</sub> = 23.65 μg/mL). Compounds <b>7d</b>, <b>10d</b>, and <b>10j</b> displayed a more pronounced nonchoice antifeedant\neffect (AFC<sub>50</sub> = 9.48, 9.14, and 12.41 μg/mL, respectively)\nthan honokiol (AFC<sub>50</sub> = 54.81 μg/mL) on P. xylostella. Moreover, compounds <b>7b</b>, <b>7″a</b>, <b>9</b>, <b>10d</b>, <b>10f</b>, and <b>10j</b> showed better growth inhibitory\nactivity against M. separata (LC<sub>50</sub> = 0.36, 0.34, 0.28, 0.16, 0.26, and 0.11 mg/mL, respectively)\nthan honokiol, toosendanin, and rotenone (LC<sub>50</sub> = 1.48,\n0.53, and 0.46 mg/mL, respectively). A potted plant assay under greenhouse\nconditions illustrated that compounds <b>10d</b> and <b>10j</b> continued to provide good control efficacy against P. xylostella and an apparent protective effect on\nplants. Further cytotoxicity assay revealed that the aforementioned\npotent compounds showed relatively moderate toxicity and a good safety\nprofile for non-target mammalian cells. Overall, the current work\nprovides valuable insight into the agrochemical innovation of honokiol-derived\nanalogs for use as natural-inspired pesticides in agricultural pest\nmanagement.