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Chinese Journal of Organic Chemistry >

2020 , Vol. 40 >Issue 7: 2035 - 2044

DOI: https://doi.org/10.6023/cjoc202002039

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

  • Du Chuanqian ,
  • Xie Baohua ,
  • He Ming ,
  • Hu Zhiye ,
  • Liu Yu ,
  • He Xue ,
  • Liu Fanyu ,
  • Cheng Chen ,
  • Zhou Hai-Bing ,
  • Huang Shengtang ,
  • Dong Chun'e
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  • 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 date: 2020-02-27

  Revised date: 2020-04-11

  Online 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).

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Abstract

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

Cite this article

Du Chuanqian , Xie Baohua , He Ming , Hu Zhiye , Liu Yu , He Xue , Liu Fanyu , Cheng Chen , Zhou Hai-Bing , Huang Shengtang , Dong Chun'e . Design, Synthesis and Biological Evaluation of Pyrano[2,3-b]-naphthoquinone Derivatives as Acetylcholinesterase Inhibitors[J]. Chinese Journal of Organic Chemistry, 2020 , 40(7) : 2035 -2044 . DOI: 10.6023/cjoc202002039

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