Chinese Journal of Organic Chemistry ›› 2023, Vol. 43 ›› Issue (8): 2790-2799.DOI: 10.6023/cjoc202302012 Previous Articles     Next Articles

5-硝基亚氨基[1,4-2H]-1,2,4-三唑啉烯式吡虫啉类似物的合成及生物活性研究

刘敏a,†, 杨冬燕b,†, 肖玉梅a,*(), 苏旺苍c, 赵峰海a, 覃兆海a,*()   

  1. a 中国农业大学理学院 北京 100193
    b 仲恺农业工程学院化学化工学院 广州 510225
    c 河南省农业科学院植物保护研究所 郑州 450002
  • 收稿日期:2023-02-12 修回日期:2023-04-04 发布日期:2023-06-26
  • 作者简介:
    †共同第一作者
  • 基金资助:
    国家重点研发计划(2016YFD0300709); 广州市科技计划(202102020214)

Synthesis and Bioactivities of 5-Nitroimino-[1,4-2H]-1,2,4-triazolines as Olefin-Imidacloprid Mimics

Min Liua,†, Dongyan Yangb,†, Yumei Xiaoa(), Wangcang Suc, Fenghai Zhaoa, Qin Zhaohai .a()   

  1. a College of Science, China Agricultural University, Beijing, 100193
    b College of Chemistry and Chemical Engineering, Zhongkai University of Agriculture and Engineering, Guangzhou 510225
    c Institute of Plant Protection, Henan Academy of Agricultural Sciences, Zhengzhou 450002
  • Received:2023-02-12 Revised:2023-04-04 Published:2023-06-26
  • Contact: *E-mail: qinzhaohai@263.net; xiaoyumei@cau.edu.cn
  • About author:
    †These authors contributed equally to this work
  • Supported by:
    The National Key Research and Development Plan of China(2016YFD0300709); The Guangzhou Science and Technology Plan(202102020214)

Olefin-imidacloprid is a highly active metabolite of imidacloprid. To solve the problem of high bee toxicity of olefin-imidacloprid, according to the bioisosterism, a series of novel olefin-imidacloprid mimics containing 1,3-disubstituted- 1,2,4-triazoline were designed and synthesized. The insecticidal activity of these compounds against A. craccivora, Nilaparvata lugens and F. occidentalis and in vitro antifungal activity were determined. The results showed that these compounds showed certain insecticidal activity at 400 μg/mL and 100% lethal rate was obtained from compound Ⅱ-7 at 100 μg/mL against F. occidentalis. The toxicity of some compounds to bees was predicted by admetSAR, and they showed low level of toxicity. On the other hand, the target compounds showed different degrees of antifungal activity against 9 plant pathogenic fungi at the concentration of 50 μg/mL. Compound I-15 exhibited the highest activity with the inhibition rate higher or equal to hymexazol against five pathogens. The structure-activity relationship analysis showed that the compounds bearing alkyl substituent at site 3 in triazoline unit displayed higher insecticidal activity than that of an aryl substitution, meanwhile, the more lipophilic groups, the higher fungicidal activity. The substitution of pyridine ring or thiazole ring at site 1 in triazoline unit had little effect on their antifungal activity. The molecular docking results showed that the binding pattern of compound Ⅱ-7 to acetylcholine binding protein (AChBP) was similar to that of imidacloprid (IMI), indicating that these compounds also had the potential to bind to AChBP, which provided a new reference for further molecular optimization.

Key words: bioisosterism, 5-nitroimine-1,2,4 triazoline, insecticidal activity, fungicidal activity, molecular docking