Novel coumarin derivatives bearing N-benzyl pyridinium moiety: Potent and dual binding site acetylcholinesterase inhibitors

被引：125

作者：

Alipour, Masoumeh ^{[2
]}

Khoobi, Mehdi ^{[1
,3
]}

Foroumadi, Alireza ^{[1
,3
]}

Nadri, Hamid ^{[4
]}

Moradi, Alireza ^{[4
]}

Sakhteman, Amirhossein ^{[4
]}

Ghandi, Mehdi ^{[2
]}

Shafiee, Abbas ^{[1
,3
]}

机构：

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

[2] Univ Tehran, Univ Coll Sci, Sch Chem, Tehran, Iran

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

[4] Shahid Sadoughi Univ Med Sci, Fac Pharm, Dept Med Chem, Yazd 8915173143, Iran

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2012年 / 20卷 / 24期

基金：

美国国家卫生研究院; 美国国家科学基金会;

关键词：

Coumarin; Benzylpyridinium; Actylcholinesterase inhibitor; Ellman's method; ALZHEIMERS-DISEASE; CHOLINERGIC HYPOTHESIS; BIOLOGICAL EVALUATION; BUTYRYLCHOLINESTERASE; DESIGN; SERIES;

D O I：

10.1016/j.bmc.2012.08.052

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

A novel series of coumarin derivatives linked to benzyl pyridinium group were synthesized and biologically evaluated as inhibitors of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The enzyme inhibitory activity of synthesized compounds was measured using colorimetric Ellman's method. It was revealed that compounds 3e, 3h, 3l, 3r and 3s have shown higher activity compared with donepezil hydrochloride as standard drug. Most of the compounds in these series had nanomolar range IC50 in which compound 3r (IC50 = 0.11 nM) was the most active compound against acetylcholinesterase enzyme. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：7214 / 7222

页数：9

共 45 条

[1]

A review on coumarins as acetylcholinesterase inhibitors for Alzheimer's disease [J].