Synthesis and biological evaluation of a new series of berberine derivatives as dual inhibitors of acetylcholinesterase and butyrylcholinesterase

被引：58

作者：

Huang, Ling ^{[1
]}

Luo, Zonghua ^{[1
]}

He, Feng ^{[1
]}

Lu, Jing ^{[1
]}

Li, Xingshu ^{[1
]}

机构：

[1] Sun Yat Sen Univ, Sch Pharmaceut Sci, Ind Inst Fine Chem & Synthet Drugs, Guangzhou 510006, Guangdong, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2010年 / 18卷 / 12期

关键词：

Synthesis and biological evaluation; Dual inhibitors; Acetylcholinesterase; Molecular modeling; CHOLINESTERASE-INHIBITORS; ALZHEIMERS-DISEASE; POTENT; DRUGS;

D O I：

10.1016/j.bmc.2010.04.063

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A series of novel berberine derivatives were designed, synthesized, and biologically evaluated as inhibitors of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Among these derivatives, compound 48a, berberine linked with 3-methylpyridinium by a 2-carbon spacer, was found to be a potent inhibitor of AChE, with an IC50 value of 0.048 mu M and compound 40c, berberine linked with 2-thionaphthol by a 4-carbon spacer, acted as the most potent inhibitor for BuChE with an IC50 value of 0.078 mu M. Kinetic studies and molecular modeling simulations of the AChE-inhibitor complex indicated that a mixed-competitive binding mode existed for these berberine derivatives. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：4475 / 4484

页数：10

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