Chinese Journal of Organic Chemistry ›› 2022, Vol. 42 ›› Issue (5): 1527-1536.DOI: 10.6023/cjoc202112021 Previous Articles     Next Articles

Special Issue: 有机氟化学虚拟合辑



王长凯, 孙腾达, 张学博, 杨新玲, 路星星, 徐欢, 石发胜, 张莉, 凌云*()   

  1. 中国农业大学理学院 应用化学系 北京 100193
  • 收稿日期:2021-12-16 修回日期:2022-01-04 发布日期:2022-01-20
  • 通讯作者: 凌云
  • 基金资助:
    国家自然科学基金(22077137); 国家自然科学基金(21472236)

Design, Synthesis and Bioactivity of Novel Fluoropyrazole Hydrazides

Changkai Wang, Tengda Sun, Xuebo Zhang, Xinling Yang, Xingxing Lu, Huan Xu, Fasheng Shi, Li Zhang, Yun Ling()   

  1. Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193
  • Received:2021-12-16 Revised:2022-01-04 Published:2022-01-20
  • Contact: Yun Ling
  • Supported by:
    National Natural Science Foundation of China(22077137); National Natural Science Foundation of China(21472236)

Laccase is a potential target and has important physiological functions in micro organisms. In order to find compounds with high laccase inhibitory activity, 15 cinnamaldehyde hydrazide derivatives containing difluoromethylpyrazole were designed and synthesized by using the principle of active substructure splicing with 4-chlorocinnamaldehyde thiosemicarbazone (PMDD-5Y) as the lead compound. The structures of the compounds were confirmed by 1H NMR, 13C NMR and HRMS. The results of laccase inhibitory activity test showed that all the prepared compounds have good activity, and N'- ((Z)-3-(3,4-dichlorophenyl)-3-phenylallylidene)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carbohydrazide (5l) and N'-((Z)- 3-(2-chlorophenyl)-3-(4-chlorophenyl)allylidene)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carbohydrazide (5m) had the half-maximal inhibiting concentration (IC50) values of 0.069 and 0.063 mmol/L, respectively, which were significantly better than that of lead compound PMDD-5Y (IC50=0.553 mmol/L) and positive control cysteine (IC50=0.298 mmol/L). The in vitro bioassay showed that the compounds with good laccase inhibitory activity showed certain fungicidal activity against V. mali, F. graminearum and M. grisea at a concentration of 50 μg/mL. In vivo trials against M. grisea demonstrated that compound 5l was effective with curative activity of 78.55% at a concentration of 200 μg/mL, which showed a certain control efficiency in vivo. Further molecular docking study revealed that compound 5l with high laccase inhibitory activity had a good protein binding mode with laccase protein.

Key words: laccase, laccase inhibitor, fluoropyrazole fragment, molecular docking, fungicidal activity