Improving Insecticidal Activity of Chlorantraniliprole by Replacing the Chloropyridinyl Moiety with a Substituted Cyanophenyl Group

作者：Zhenwu Yu, Xiulan Zhang, Jinzhou Ren, Haolin Yuan, Wei Gao, Lixia Xiong, Na Yang, Yuxin Li, Zhengming Li, Zhijin Fan · 发表于：Journal of Agricultural and Food Chemistry · 年份：2022 · DOI：10.1021/acs.jafc.2c03133 · 被引用次数：33 · 研究领域：Insect and Pesticide Research、Insect Pest Control Strategies、Insect Resistance and Genetics

Insect ryanodine receptors (RyRs) are molecular targets of the anthranilic diamide insecticides. In the present study, a new series of anthranilic diamides containing a cyanophenyl pyrazole moiety were rationally designed by active-fragment assembly and computer-aided design using the 3D structure of Plutella xylostella RyRs as a receptor and chlorantraniliprole as a ligand. Most of the titled compounds showed good toxicity against Mythimna separate, P. xylostella, and Spodoptera frugiperda . Compounds CN06, CN11, and CN16 with corresponding LC 50 values of 0.15, 0.29, and 0.52 mg·L –1, respectively, against M. separate showed comparable activity to that of chlorantraniliprole (0.13 mg·L –1 ). Surprisingly, CN06, CN11, and CN16 with corresponding LC 50 values of 1.6 × 10 –5, 3.0 × 10 –5, and 2.8 × 10 –5 mg·L –1, respectively, against P. xylostella were at least 5-fold more active than chlorantraniliprole (1.5 × 10 –4 mg·L –1 ). In the case of S. frugiperda, CN06, CN11, and CN16 had good potency but lower than chlorantraniliprole in terms of LC 50 values (0.58, 0.54, and 0.56 mg·L –1 versus 0.31 mg·L –1 ). Molecular docking of CN06 and chlorantraniliprole to P. xylostella RyRs validated the molecular design, and the calcium imaging technique further proved the potential target of CN06 as RyRs. Compounds CN06, CN11, and CN16 could be more effective than chlorantraniliprole in targeting the resistant RyR mutants of S. frugiperda (G4891E, I4734M) through the binding mode and ener...