Chinese Journal of Organic Chemistry ›› 2020, Vol. 40 ›› Issue (7): 2035-2044.DOI: 10.6023/cjoc202002039 Previous Articles     Next Articles


杜川黔a, 谢宝花a, 贺明a, 胡志烨a, 刘豫a, 何雪a, 刘凡玉a, 程晨c, 周海兵a, 黄胜堂b, 董春娥a   

  1. a 武汉大学药学院 湖北省有机氟类药物工程技术研究中心 武汉 430071;
    b 湖北科技学院药学院 心脑血管代谢紊乱实验室 湖北咸宁 437100;
    c 武汉大学生命科学学院 武汉 430072
  • 收稿日期:2020-02-27 修回日期:2020-04-11 发布日期:2020-04-23
  • 通讯作者: 周海兵, 黄胜堂, 董春娥;;
  • 基金资助:

Design, Synthesis and Biological Evaluation of Pyrano[2,3-b]-naphthoquinone Derivatives as Acetylcholinesterase Inhibitors

Du Chuanqiana, Xie Baohuaa, He Minga, Hu Zhiyea, Liu Yua, He Xuea, Liu Fanyua, Cheng Chenc, Zhou Hai-Binga, Huang Shengtangb, Dong Chun'ea   

  1. a Hubei Province Engineering and Technology Research Centre for Fluorinated Pharmaceuticals, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071;
    b Laboratory of Cardiovascular, Cerebrovascular and Metabolic Disorder, Hubei University of Science and Technology, Xianning, Hubei 437100;
    c College of Life Sciences, Wuhan University, Wuhan 430072
  • Received:2020-02-27 Revised:2020-04-11 Published:2020-04-23
  • Supported by:
    Project supported by the National Natural Science Foundation of China (No. 81773557), the Major Project of Technology Innovation Program of Hubei Province (No. 2018ACA123) and the Open Project of the Diabetes Key Laboratory of Hubei University of Science and Technology (No. 2020-21XZ002).

A novel synthetic methodology was developed and a series of pyrano[2,3-b]naphthoquinone derivatives were designed and synthesized in excellent yields. Most of these compounds showed effective anti-AChE activities and high selectivity for acetylcholinesterase (AChE) over butyrylcholinesterase (BuChE). Among them, (2-Amino-4-(3-cyanophenyl)-5,10-dioxo-5,10-dihydro-4H-benzo[g]chromene-3-carbonitrile) (3n) was significantly potent, with an IC50 value of 1.22 μmol/L for AChE, which was 164-fold higher than butyrylcholinesterase (BuChE) in vitro. Moreover, molecular modeling provides valuable information for understanding the potency and selectivity of this kind of compounds for AChE. Consequently, these potent and highly selective AChE inhibitors are potential leads for development of the drug for treatment of Alzheimer's disease.

Key words: pyrano[2,3-b]naphthoquinone, acetylcholinesterase (AChE) inhibitor, Alzheimer's disease, molecular modeling