State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, PR China.
Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin 300071, PR China.
J Agric Food Chem. 2022 Dec 21;70(50):15665-15681. doi: 10.1021/acs.jafc.2c05738. Epub 2022 Dec 12.
Pests are one of the major factors causing crop damage and food security problems worldwide. Based on our previous studies on the discovery of insecticidal leads targeting the ryanodine receptors (RyRs), a three-dimensional quantitative structure-activity relationship (3D-QSAR) model was established to design and synthesize a series of anthranilic diamides containing a halogenated phenyl 3-trifluoroethoxypyrazole moiety. The preliminary bioassays disclosed that , , and against showed comparable activity to chloranthraniliprole (LC: 0.16, 0.16, 0.14, and 0.13 mg·L, respectively). More than half of the target compounds displayed good activity against where was the most active compound, 25 times more active than chloranthraniliprole (LC: 6.0 × 10 versus 1.5 × 10 mg·L). For , displayed slightly inferior potency to chlorantraniliprole (LC: 0.47 versus 0.31 mg·L). For RyR mutants of (G4891E, I4734M), compound could show higher affinity than chlorantraniliprole according to the binding mode and energy in molecular docking experiments. Calcium imaging technique, molecular docking, density functional theory calculations, and electrostatic potential studies validated that the RyR was the target of the most active candidate , which deserves further development.
害虫是导致全球作物受损和粮食安全问题的主要因素之一。基于我们之前关于发现针对肌质网 Ca2+ 释放通道（RyR）的杀虫先导物的研究，建立了一个三维定量构效关系（3D-QSAR）模型，用于设计和合成一系列含卤素苯 3-三氟乙氧基吡唑部分的邻苯二甲酰胺。初步的生物测定结果表明，化合物 、 、 和 对 表现出与氯虫苯甲酰胺（LC：0.16、0.16、0.14 和 0.13 mg·L，分别）相当的活性。超过一半的目标化合物对 表现出良好的活性，其中 最为活跃，活性是氯虫苯甲酰胺的 25 倍（LC：6.0×10 对 1.5×10 mg·L）。对于 ，化合物 显示出比氯虫苯甲酰胺稍差的效力（LC：0.47 对 0.31 mg·L）。对于 RyR 的突变体 （G4891E、I4734M），根据分子对接实验中的结合模式和能量，化合物 可以显示出比氯虫苯甲酰胺更高的亲和力。钙成像技术、分子对接、密度泛函理论计算和静电势研究验证了 RyR 是最活跃的候选物 ，这值得进一步开发。
