Linear Peptidomimetics Containing Isoxazoline Scaffold: Design, Synthesis, Bioevaluation as Efficient Insecticidal...

A series of structurally novel polysubstituted linear peptidomimetics hybridizing arylisoxazoline heterocycles were designed and synthesized via a four-component one-pot method based on green synthetic strategies. The structures of the obtained compounds were confirmed by satisfied spectral analyses including ¹H NMR, ¹³C NMR and ESI-MS. Bioassays indicated that most of the target compounds exhibited superior insecticidal activity against lepidopteran pests such as Plutella xylostella and Helicoverpa armigera at a concentration of 100 μg/mL compared to the reference insecticides Chlorfenapyr and Chlorantraniliprole. Notably, compound JK-10 showed outstanding performance, achieving 100% mortality against L0 and L1 larvae at 0.195 μg/mL and demonstrating higher activity than that of Chlorantraniliprole. Density functional theory (DFT) calculations and molecular docking studies suggested that these compounds may possess strong binding affinity to the γ-aminobutyric acid (GABA) receptor, indicating their potential as novel GABA receptor inhibitors for the integrated management of lepidopteran pests in agriculture.