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  • 标题:Synthesis of Amide and Ester Derivatives of Cinnamic Acid and Its Analogs: Evaluation of Their Free Radical Scavenging and Monoamine Oxidase and Cholinesterase Inhibitory Activities
  • 本地全文:下载
  • 作者:Koichi Takao ; Kazuhiro Toda ; Takayuki Saito
  • 期刊名称:Chemical and Pharmaceutical Bulletin
  • 印刷版ISSN:0009-2363
  • 电子版ISSN:1347-5223
  • 出版年度:2017
  • 卷号:65
  • 期号:11
  • 页码:1020-1027
  • DOI:10.1248/cpb.c17-00416
  • 语种:English
  • 出版社:The Pharmaceutical Society of Japan
  • 摘要:

    A series of cinnamic acid derivatives, amides ( 1 – 12 ) and esters ( 13 – 22 ), were synthesized, and structure–activity relationships for antioxidant activity, and monoamine oxidases (MAO) A and B, acetylcholinesterase, and butyrylcholinesterase (BChE) inhibitory activities were analyzed. Among the synthesized compounds, compounds 1 – 10 , 12 – 18 , and rosmarinic acid ( 23 ), which contained catechol, o -methoxyphenol or 5-hydroxyindole moieties, showed potent 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity. Compounds 9 – 11 , 15 , 17 – 22 showed potent and selective MAO-B inhibitory activity. Compound 20 was the most potent inhibitor of MAO-B. Compounds 18 and 21 showed moderate BChE inhibitory activity. In addition, compound 18 showed potent antioxidant activity and MAO-B inhibitory activity. In a comparison of the cinnamic acid amides and esters, the amides exhibited more potent DPPH free radical scavenging activity, while the esters showed stronger inhibitory activities against MAO-B and BChE. These results suggested that cinnamic acid derivatives such as compound 18 , p -coumaric acid 3,4-dihydroxyphenethyl ester, and compound 20 , p -coumaric acid phenethyl ester, may serve as lead compounds for the development of novel MAO-B inhibitors and candidate lead compounds for the prevention or treatment of Alzheimer’s disease.

  • 关键词:cinnamic acid amide;cinnamic acid ester;monoamine oxidase;cholinesterase;antioxidant;Alzheimer’s disease
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