李秀珍, 靳彬艳, 崔佳琳, 冯彦姣, 张晓鸣, 张莉. 1-苯基-5-氨基吡唑类蜕皮激素类似物的合成与杀虫活性[J]. 农药学学报, 2024, 26(3): 451-461. DOI: 10.16801/j.issn.1008-7303.2024.0042
    引用本文: 李秀珍, 靳彬艳, 崔佳琳, 冯彦姣, 张晓鸣, 张莉. 1-苯基-5-氨基吡唑类蜕皮激素类似物的合成与杀虫活性[J]. 农药学学报, 2024, 26(3): 451-461. DOI: 10.16801/j.issn.1008-7303.2024.0042
    LI Xiuzhen, JIN Binyan, CUI Jialin, FENG Yanjiao, ZHANG Xiaoming, ZHANG Li. Synthesis and insecticidal activity of 1-phenyl-5-aminopyrazole ecdysteroid analogs[J]. Chinese Journal of Pesticide Science, 2024, 26(3): 451-461. DOI: 10.16801/j.issn.1008-7303.2024.0042
    Citation: LI Xiuzhen, JIN Binyan, CUI Jialin, FENG Yanjiao, ZHANG Xiaoming, ZHANG Li. Synthesis and insecticidal activity of 1-phenyl-5-aminopyrazole ecdysteroid analogs[J]. Chinese Journal of Pesticide Science, 2024, 26(3): 451-461. DOI: 10.16801/j.issn.1008-7303.2024.0042

    1-苯基-5-氨基吡唑类蜕皮激素类似物的合成与杀虫活性

    Synthesis and insecticidal activity of 1-phenyl-5-aminopyrazole ecdysteroid analogs

    • 摘要: 为开发结构新颖的高效昆虫生长调节剂,以蜕皮激素受体 (EcR) 为靶标,以课题组前期发现的高活性化合物 I7 (N-(4-氰基-1-苯基-1H-吡唑-5-基)-2-苯乙酰胺) 为先导,设计合成了20 个 1-苯基-5-氨基吡唑类化合物,结构均经核磁共振氢谱 (1H NMR)、核磁共振碳谱 (13C NMR) 和高分辨质谱 (HRMS) 确证。杀虫活性测定结果表明,化合物 M10M17M18 在250 mg/L 质量浓度下对小菜蛾 Plutella xylostella 致死率较先导化合物 I7 (60%) 提高了20%以上,其中化合物 M10 活性最佳,在 125 mg/L 质量浓度下对小菜蛾致死率 (60%) 略低于相同质量浓度下商品化药剂虫酰肼 (70%),且其处理后的小菜蛾呈现出典型蜕皮激素类似物中毒症状;小菜蛾蜕皮激素受体(P. xylostella EcR,PxEcR)靶标结合活性结果表明,化合物 M2M6M9M12M13M15M20 的靶标结合活性均优于化合物 I7,其中化合物 M15 (IC50(PxEcR) = 2.02 μmol/L) 的靶标结合活性是化合物 I7 (IC50(PxEcR) = 23.21 μmol/L) 的 11.5 倍;通过分子对接、分子动力学模拟等方法进一步分析了化合物 I7、M10M15 与 EcR 受体的结合作用机制,可为后续靶向 EcR 的昆虫生长调节剂研究提供参考。

       

      Abstract: To develop highly efficient and structurally novel insect growth regulators, 20 1-phenyl-5-amino pyrazoles were designed and synthesized using ecdysteroid receptor (EcR) as the target and I7 (N-(4-cyano-1-phenyl-1H-pyrazol-5-yl)-2-phenylacetamide), a highly active compound discovered by our group, as a lead. All synthesized structures were confirmed by 1H NMR, 13C NMR and HRMS. The insecticidal activity of the compounds showed that the lethality of compounds M10, M17 and M18 was more than 20% higher than that of lead compound I7 (60%) at a concentration of 250 mg/L. Compound M10 was the most active, exhibiting a lethality rate of 60% at 125 mg/L, which is slightly lower than that of the commercial tebufenozide (70%), and Plutella xylostella treated with this compound showed typical symptoms of ecdysteroid analogue poisoning. The results of the target binding activity of P. xylostella EcR(PxEcR) showed that the compounds M2, M6, M9, M12, M13, M15 and M20 were better than that of compound I7, and that the target binding activity of compound M15 (IC50(PxEcR) = 2.02 μmol/L) was 11.5 times higher than that of compound I7 (IC50(PxEcR) = 23.21 μmol/L). The binding mechanism between compounds I7, M10, M15 and EcR receptor was further analyzed by molecular docking and molecular dynamics simulation, which will provide guidance for the further research on insect growth regulators targeting EcR.

       

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