Design, Synthesis And Insecticidal Activity Of Novel Isoxazoline Derivatives Containing Acylthiourea Structur

Isoxazolines are of great interest because of their unique mode of action and excellent activity against lepidopteran pests.Effective agents with novel modes of action for the control of Plutella xylostella and Spodoptera frugiperda were developed.This was achieved by designing and synthesizing thirty-two isoxazoline derivatives containing acylthiourea moieties as active units.The insecticidal activities of the compounds were tested by the leaf-dip method and diet surface overlay method against the moths.Compound 32 was identified as the optimal compound by establishing a 3D-QSAR model based on the activity test results.The model was used to guide the optimization of the compound’s structure.The mechanism of action of compound 32 was initially investigated by enzyme activity assay,molecular docking assay and proteomics assay.The main studies are as follows:1.Thirty-two isoxazoline derivatives containing acylthiourea moieties were designed and prepared,and these target compounds were tested for their insecticidal activity against Plutella xylostella and Spodoptera frugiperda,and structurally characterized by ¹H NMR,¹³C NMR and HRMS.2.The results of the activity tests showed that the LC₅₀of compound 32 was0.26 mg/L against Plutella xylostella,which was better than that of the positive control ethiprole(LC₅₀=3.81 mg/L)and compounds 1-31;the LC₅₀of compound 32was 1.58 mg/L against Spodoptera frugiperda,which was better than that of the positive control chlorantraniliprole(LC₅₀=1.61 mg/L)and compounds 1-31.3.The insect GABA ELISA showed that compound 32 up-regulated the GABA content of Plutella xylostella.The molecular docking assay further elucidated the compound’s mode of action with the GABA receptor.The experimental results were similar to those of ethiprole,indicating that compound 32 might act on the GABA receptor.4.In the proteomics analysis,compound 32 down-regulated the expression of mitochondrial cytochrome C protein in the oxidative phosphorylation pathway of Plutella xylostella,which impedes the electron transfer of the respiratory chain of the mitochondrial energy metabolic system of Plutella xylostella.Therefore,compound32 may act on the GABA receptor of Plutella xylostella,thus releasing the inhibitory neurotransmitter GABA,which transmits respiratory inhibition signals and eventually leads to the death of Plutella xylostella due to respiratory inhibition.