Synthesis and anti-cholinesterase activity of new 7-hydroxycoumarin derivatives

被引：77

作者：

Alipour, Masoumeh ^{[1
,2
]}

Khoobi, Mehdi ^{[1
,2
]}

Moradi, Alireza ^{[3
]}

Nadri, Hamid ^{[3
]}

Moghadam, Farshad Homayouni ^{[4
]}

Emami, Saeed ^{[5
,6
]}

Hasanpour, Zeinab ^{[1
,2
]}

Foroumadi, Alireza ^{[1
,2
]}

Shafiee, Abbas ^{[1
,2
]}

机构：

[1] Univ Tehran Med Sci, Fac Pharm, Dept Med Chem, Tehran 14176, Iran

[2] Univ Tehran Med Sci, Pharmaceut Sci Res Ctr, Tehran 14176, Iran

[3] Shahid Sadoughi Univ Med Sci, Fac Pharm, Yazd, Iran

[4] Shahid Sadoughi Univ Med Sci, Sch Med, Neurobiomed Res Ctr, Yazd, Iran

[5] Mazandaran Univ Med Sci, Fac Pharm, Dept Med Chem, Sari, Iran

[6] Mazandaran Univ Med Sci, Pharmaceut Sci Res Ctr, Sari, Iran

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2014年 / 82卷

基金：

美国国家科学基金会;

关键词：

Alzheimer's disease; Acetylcholinesterase; Coumarins; Docking study; ALZHEIMERS-DISEASE; BIOLOGICAL EVALUATION; COUMARIN DERIVATIVES; ACETYLCHOLINESTERASE; INHIBITORS; BEARING; DOCKING; POTENT; ACETYL; BUTYRYLCHOLINESTERASE;

D O I：

10.1016/j.ejmech.2014.05.056

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 7-hydroxycoumarin derivatives connected by an amidic linker to the different amines were designed and synthesized as cholinesterase inhibitors. Most compounds showed remarkable inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Among them, N-(1-benzylpiperidin-4-yl)acetamide derivative 4r with IC50 value of 1.6 mu M was the most potent compound against AChE. The selectivity index of compound 4r for anti-AChE activity was about 26. Moreover, the compound 4r significantly protected PC12 neurons against H2O2-induced cell death at low concentrations. The docking study of compound 4r with AChE enzyme showed that both CAS and PAS are occupied by the ligand. (C) 2014 Elsevier Masson SAS. All rights reserved.

引用

页码：536 / 544

页数：9

共 28 条

[1]

Akrami H., 2014, EUR J MED C IN PRESS

[2] Synthesis of Some New 3-Coumaranone and Coumarin Derivatives as Dual Inhibitors of Acetyl- and Butyrylcholinesterase [J].