Design, Synthesis, and Evaluation of Multitarget-Directed Selenium-Containing Clioquinol Derivatives for the Treatment of Alzheimer's Disease

被引：98

作者：

Wang, Zhiren ^{[1
]}

Wang, Yali ^{[1
]}

Li, Wenrui ^{[1
]}

Mao, Fei ^{[1
]}

Sun, Yang ^{[1
]}

Huang, Ling ^{[1
]}

Li, Xingshu ^{[1
]}

机构：

[1] Sun Yat Sen Univ, Sch Pharmaceut Sci, Inst Drug Synth & Pharmaceut Proc, Guangzhou 510275, Guangdong, Peoples R China

来源：

ACS CHEMICAL NEUROSCIENCE | 2014年 / 5卷 / 10期

关键词：

Alzheimers disease; selenium-containing clioquinol derivatives; antioxidative properties; inhibition of metal-induced A beta aggregation; AMYLOID-BETA; NEURODEGENERATIVE DISEASES; BIOLOGICAL EVALUATION; ANTIOXIDANT ACTIVITY; IRON; TARGET; COPPER; ACETYLCHOLINESTERASE; AGGREGATION; GLUTATHIONE;

D O I：

10.1021/cn500119g

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 selenium-containing clioquinol derivatives were designed, synthesized, and evaluated as multifunctional anti-Alzheimer's disease (AD) agents. In vitro examination showed that several target compounds exhibited activities such as inhibition of metal-induced A beta aggregation, antioxidative properties, hydrogen peroxide scavenging, and the prevention of copper redox cycling. A parallel artificial membrane permeation assay indicated that selenium-containing clioquinol derivatives possessed significant blood-brain barrier (BBB) permeability. Compound 8a, with a propynylselanyl group linked to the oxine, demonstrated higher hydrogen peroxide scavenging and intracellular antioxidant activity than clioquinol. Furthermore, 8a exhibited significant inhibition of Cu(II)-induced A beta 1-42 aggregation and was capable of disassembling the preformed Cu(II)-induced A beta aggregates. Therefore, 8a is an excellent multifunctional promising compound for development of novel drugs for AD.

引用

页码：952 / 962

页数：11

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