Chinese Journal of Organic Chemistry ›› 2020, Vol. 40 ›› Issue (2): 478-488.DOI: 10.6023/cjoc201907043 Previous Articles     Next Articles


李英俊a, 刘雪洁a, 刘季红b, 高立信c, 靳焜d, 盛丽c, 杨鸿境a, 林乐弟a, 李佳c   

  1. a 辽宁师范大学化学化工学院 大连 116029;
    b 大连理工大学化学分析测试中心 大连 116023;
    c 中国科学院上海药物研究所 国家新药筛选中心 药物研究国家重点实验室 上海 201203;
    d 大连理工大学精细化工国家重点实验室 大连 116012
  • 收稿日期:2019-07-27 修回日期:2019-09-09 发布日期:2019-10-09
  • 通讯作者: 李英俊, 李佳;
  • 基金资助:

Synthesis and Protein Tyrosine Phosphatase 1B (PTP1B) Inhibitory Activity Evaluation of Novel Carbazole-Based Carbohydrazone Derivatives

Li Yingjuna, Liu Xuejiea, Liu Jihongb, Gao Lixinc, Jin Kund, Sheng Lic, Yang Hongjinga, Lin Ledia, Li Jiac   

  1. a College of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029;
    b Chemistry Analysis and Inspection Center, Dalian University of Technology, Dalian 116023;
    c National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203;
    d State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116012
  • Received:2019-07-27 Revised:2019-09-09 Published:2019-10-09
  • Supported by:
    Project supported by the Natural Science Foundation of Liaoning Province (No. 20102126).

A series of novel carbazole-based mono-/bis-carbohydrazone derivatives 3 and 4 were synthesized. Their structures were characterized by 1H NMR, 13C NMR, IR spectra and elemental analysis. The inhibitory activities of all synthesized compounds against protein tyrosine phosphatase 1B (PTP1B) were evaluated, and the structure-activity relationship was discussed. The results indicated that most of the compounds had good inhibitory activity against PTP1B, and 1,5-bis[(9-butyl-3-carba-zolyl)methylene]carbohydrazone (4c) showed the highest inhibitory activity against PTP1B with IC50=(4.81±0.41) μmol/L and the activity was higher than that of the control drug oleanolic acid. Molecular docking and density functional theory (DFT) calculations of 3f and 4c were carried out. The results of molecular docking indicated that 1-[(9-heptyl-3-carbazolyl)meth-ylene]carbohydrazone (3f) and 4c bind to an active site of PTP1B enzyme formed by the helices α3 and α6, and formed a stable complex respectively with PTP1B enzyme by hydrogen bonds, polar, hydrophobic and π-π interactions.

Key words: carbohydrazone, carbazole, synthesis, PTP1B inhibitor, molecular docking, DFT calculations