Design, Synthesis, and Insecticidal Activity of Novel Isoxazoline Compounds That Contain <i>Meta</i>-diamides against Fall Armyworm (Spodoptera frugiperda)

Fall armyworm (Spodoptera frugiperda) is a major migratory pest around the entire world that causes severe damage to agriculture. We designed and synthesized a series of novel isoxazoline derivatives based on the previously discovered active compound H13 to find new and effective candidates against S. frugiperda. Most of them showed excellent insecticidal activity. In addition, a three-dimensional quantitative structure–activity relationship model was established, and compound F32 was designed and synthesized based on the results. The bioassay result showed that compound F32 exhibited excellent activity against S. frugiperda (LC50 = 3.46 mg/L), which was substantially better than that of the positive control fipronil (LC50 = 78.8 mg/L). Furthermore, an insect γ-aminobutyric acid (GABA) enzyme-linked immunosorbent assay indicated that F32 can upregulate the content of GABA in insects in a manner similar to that of fipronil. Molecular docking showed that the hydrophobic effect and hydrogen-bond interactions are vital factors between the binding of F32 and receptors. All of these results suggest that compound F32 could be employed as a novel isoxazoline lead compound to control S. frugiperda

Discovery of Novel Isoxazoline Compounds that Incorporate a <i>para</i>-Diamide Moiety as Potential Insecticidal Agents against Fall Armyworm (Spodoptera frugiperda)

Spodoptera frugiperda is a major migratory agricultural pest, which seriously impedes agricultural production around the world. To discover potent compounds against S. frugiperda, a number of novel isoxazoline derivatives were designed and synthesized and created on account of the identified lead compound F32 (4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methyl-N-(3-propionamidophenyl)benzamide). Based on the three-dimensional quantitative structure–activity relationship of those compounds, the compound G22 (N-(4-acetamidophenyl)-4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzamide) was developed. A bioassay showed that G22 is highly lethal to S. frugiperda (LC50 = 1.57 mg/L), a more effective control than insecticides fipronil (LC50 = 78.8 mg/L) and chlorantraniliprole (LC50 = 1.60 mg/L). Field trials were also implemented to identify candidate agents. Furthermore, from the insect γ-aminobutyric acid (GABA) enzyme-linked immunosorbent assay, it is obvious that G22 could up-regulate the expression of GABA of insects, which showed a similar result to fipronil. The analysis of molecular docking exhibited that the hydrophobic effect and hydrogen bonds play key roles in the combination between G22 with GABA receptors. This study provides a potent isoxazoline candidate compound for the S. frugiperda control