Design and synthesis of tacrine-ferulic acid hybrids as multi-potent anti-Alzheimer drug candidates

被引：197

作者：

Fang, Lei ^{[1
,2
]}

Kraus, Birgit ^{[3
]}

Lehmann, Jochen ^{[1
]}

Heilmann, Joerg ^{[3
]}

Zhang, Yihua ^{[2
]}

Decker, Michael ^{[1
]}

机构：

[1] Univ Jena, Lehrstuhl Pharmazeut Med Chem, Inst Pharm, D-07743 Jena, Germany

[2] China Pharmaceut Univ, Ctr Drug Discovery, Nanjing 210009, Peoples R China

[3] Univ Regensburg, Lehrstuhl Pharmazeut Biol, D-93053 Regensburg, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 09期

关键词：

tacrine; ferulic acid; cholinesterase inhibitor; antioxidant; anti-Alzheimer drug; hybrid molecule;

D O I：

10.1016/j.bmcl.2008.03.073

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Five tacrine-ferulic acid hybrids (6a-e) were designed and synthesized as multi-potent anti-Alzheimer drug candidates. All target compounds have better acetylcholinesterase inhibitory activity and comparable butyrylcholinesterase inhibitory activity in relation to tacrine. Interestingly, 6d showed a reversible and non-competitive inhibitory action for acetylcholinesterase indicating interaction with the peripheral anionic site, whereas a reversible but competitive inhibitory action for butyrylcholinesterase. The antioxidant study revealed that four target compounds have, compared to Trolox, high ability to absorb reactive oxygen species. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：2905 / 2909

页数：5

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