MEDI-500

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.

Plant pathogenic fungi seriously threaten agricultural production. There is an urgent need to develop novel fungicides with low toxicity and high efficiency. In this study, we designed and synthesized 44 pyrazolo[3,4-d]pyrimidin-4-one derivatives and evaluated them for their fungicidal activities. The bioassay data revealed that most of the target compounds possessed moderate to high in vitro antifungal activities. Especially compound g22 exhibited remarkable antifungal activity against Sclerotinia sclerotiorum with an EC₅₀ value of 1.25 mg/L, close to that of commercial fungicide boscalid (EC₅₀ = 0.96 mg/L) and fluopyram (EC₅₀ = 1.91 mg/L). Moreover, compound g22 possessed prominent protective activity against S. sclerotiorum in vivo for 24 h (95.23%) and 48 h (93.78%), comparable to positive control boscalid (24 h (96.63%); 48 h (93.23%)). Subsequent studies indicated that compound g22 may impede the growth and reproduction of S. sclerotiorum by affecting the morphology of mycelium, destroying cell membrane integrity, and increasing cell membrane permeability. In addition, the application of compound g22 did not injure the growth or reproduction of Italian bees. This study revealed that compound g22 is expected to be developed for efficient and safe agricultural fungicides.