2. Academic Validation
  3. Discovery of a polysubstituted phenyl containing novel N-phenylpyrazole scaffold as potent ryanodine receptor activator

Discovery of a polysubstituted phenyl containing novel N-phenylpyrazole scaffold as potent ryanodine receptor activator

  • Bioorg Med Chem. 2020 Dec 15;28(24):115829. doi: 10.1016/j.bmc.2020.115829.
Jingbo Liu 1,  Fengyun Li 2,  Zesheng Hao 3,  Yuanhong Wang 4,  Xuewen Hua 5,  Yuxin Li 6,  Zhengming Li 7
Affiliations

Affiliations

  • 1 College of Horticulture and Landscape Architecture, Tianjin Agricultural University, Tianjin 300384, China; State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China. Electronic address: liujingbo0626@126.com.
  • 2 College of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
  • 3 State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China.
  • 4 College of Horticulture and Landscape Architecture, Tianjin Agricultural University, Tianjin 300384, China.
  • 5 College of Agriculture, Liaocheng University, Liaocheng 252000, China.
  • 6 State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China; Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Hunan Normal University, Changsha 410125, China. Electronic address: liyx128@nankai.edu.cn.
  • 7 State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China. Electronic address: nkzml@vip.163.com.
PMID: 33191084 DOI: 10.1016/j.bmc.2020.115829
Abstract

To develop the novel ryanodine receptors (RyRs) insecticides, encouraged by our previous research work, a series of novel N-phenylpyrazole derivatives containing a polysubstituted phenyl ring scaffold were designed and synthesized. The bioassays results indicated that some title compounds exhibited excellent insecticidal activity. For oriental armyworm (Mythimna separata), compounds 7f, 7g, 7i and 7o at 0.5 mg L-1 displayed 100% larvicidal activity, and even at 0.1 mg L-1, 7o was 30% larvicidal activity, comparable to chlorantraniliprole (30%) and better than cyantraniliprole (10%). Compounds 7f and 7o had the median lethal concentrations (LC50) of 8.83 × 10-2 and 7.12 × 10-2 mg L-1, respectively, close to chlorantraniliprole (6.79 × 10-2 mg L-1). Additionally, for diamondback moth (Plutella xylostella), the larvicidal activity of compounds 7f and 7i were 90% and 70% at 0.01 mg L-1, respectively, better than chlorantraniliprole (50%) and cyantraniliprole (40%). More impressively, the LC50 value of 7f was 4.2 × 10-3 mg L-1, slightly lower than that of chlorantraniliprole (5.0 × 10-3 mg L-1). The molecular docking between compound 7f and RyRs of diamondback moth validated our molecular designation. Furthermore, the calcium imaging experiment explored the influence of compound 7o on the calcium homeostasis in the central neurons of the third larvae of oriental armyworm. The results of this study indicated that 7o is a potent novel lead targeting at RyRs.

Keywords

Calcium imaging; Insecticidal activity; Molecular docking; N-phenylpyrazole; Polysubstituted phenyl ring.

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