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

doi:10.6023/cjoc202002039

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

新型吡喃并[2,3-b]萘醌类乙酰胆碱酯酶抑制剂的设计合成及生物活性研究

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

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 E-mail:zhouhb@whu.edu.cn;cdong@whu.edu.cn;huangst6511@hbust.edu.cn
基金资助:
国家自然科学基金（No.81773557）、湖北省重大专项（No.2018ACA123）及湖北科技学院糖尿病重点实验室开放基金（No.2020-21XZ002）资助项目.

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

Du Chuanqian^a, Xie Baohua^a, He Ming^a, Hu Zhiye^a, Liu Yu^a, He Xue^a, Liu Fanyu^a, Cheng Chen^c, Zhou Hai-Bing^a, Huang Shengtang^b, Dong Chun'e^a

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).

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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.

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新型吡喃并[2,3-b]萘醌类乙酰胆碱酯酶抑制剂的设计合成及生物活性研究

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

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