Discovery of Novel (+)-Nootkatone-Based Amine Derivatives as Potential Insecticide Candidates.

To discover novel natural product-based insecticides, a series of (+)-nootkatone-based amine derivatives were prepared and evaluated for their insecticidal activities against Walker, Sulzer, and Linnaeus. Insecticidal assays showed that most of the title (+)-nootkatone derivatives exhibited stronger insecticidal activities against three insect pests than the precursor (+)-nootkatone after the introduction of amine groups on the parent (+)-nootkatone. Compounds , , , , , , and displayed more promising growth inhibitory (GI) effect against than the commercially available botanical insecticide toosendanin. Compound exhibited the most potent aphicidal activity with an LD value of 0.011 μg/larvae, which was 2.09-fold higher than the positive control rotenone. Additionally, compounds and showed more promising larvicidal activity against with LC values of 260 and 230 mg/L, respectively, superior to that of rotenone (460 mg/L). Moreover, derivatives and exhibited better control efficacy toward than rotenone under greenhouse conditions. Preliminary mechanistic studies revealed that derivative could inhibit the activity of glutathione -transferase (GST) in and thus exerted larvicidal activity, and molecular docking further demonstrated that could interact well with some amino acid residues of GST. Finally, the toxicity assay suggested that derivatives and were relatively less toxic to nontarget organisms. These findings will provide insights into the development of (+)-nootkatone derivatives as green pesticides.