2. Academic Validation
  3. Novel Nitrophenyl Substituted Anthranilic Diamide Derivatives: Design, Synthesis, Selectivity, and Antiresistance

Novel Nitrophenyl Substituted Anthranilic Diamide Derivatives: Design, Synthesis, Selectivity, and Antiresistance

  • J Agric Food Chem. 2023 Nov 22;71(46):17646-17657. doi: 10.1021/acs.jafc.3c03067.
Pengwei Sun 1,  Ze Zhang 1,  Jiahui Zhao 2,  Hongyuan Zhang 1,  Lianyun Lin 2,  Xinyao Wang 1,  Linshan Li 1,  Peng Cao 3,  Zhongwen Wang 1,  Zhengming Li 1,  Zhiguang Yuchi 2,  Yuxin Li 1 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Elemento-Organic Chemistry, Department of Chemistry, Nankai University, 94 Weijin Road, Tianjin 300071, China.
  • 2 Tianjin Key Laboratory for Modern Drug Delivery and High-Efficiency, Collaborative Innovation Center of Chemical Science and Engineering, School of Pharmaceutical Science and Technology, Tianjin University, 92 Weijin Road, Tianjin 300072, China.
  • 3 Key Laboratory of Drug Targets and Drug Leads for Degenerative Diseases, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing 210023, China.
  • 4 Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Hunan Normal University, 371 Tongzipo Road, Changsha 410013, Hunan, China.
PMID: 37939255 DOI: 10.1021/acs.jafc.3c03067
Abstract

Diamide insecticides have gained popularity due to their high efficacy and low toxicity to nontarget organisms. However, diamide-associated resistance has emerged recently, causing a significant reduction in their potency, thereby hindering sustainable agricultural development. Here, we explored novel diamide insecticide analogs and, using a structure-based approach, rationally designed and synthesized 28 nitrophenyl substituted anthranilic diamides. Most of the compounds showed moderate to good activity against Mythimna separata, Plutella xylostella, and Spodoptera frugiperda. Among them, compounds Ia and Im showed extraordinarily high activity and their mode of action was verified on isolated neurons. Additionally, Im exhibited over 10-fold greater potency than chlorantraniliprole in a HEK293 cell line stably expressing S. frugiperda ryanodine receptors (SfRyRs) containing the resistance mutations, G4891E and I4734M. The binding modes of Im in the SfRyRs were predicted using in silico molecular docking analysis. Our novel nitrophenyl substituted anthranilic diamide derivatives provide valuable insights for the design of insecticidal RyR-targeting compounds to effectively control both wild type and diamide insecticide-resistant lepidopteran pests.

Keywords

diamide insecticide; mode of action; nitrophenyl; resistance; ryanodine receptor.

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