Design, synthesis and biological evaluation of D-ring opened galantamine analogs as multifunctional anti-Alzheimer agents

被引：60

作者：

Fang, Lei ^{[1
,2
]}

Fang, Xubin ^{[1
]}

Gou, Shaohua ^{[1
]}

Lupp, Amelie ^{[3
]}

Lenhardt, Isabel ^{[3
]}

Sun, Yanyan ^{[1
]}

Huang, Zhangjian ^{[2
]}

Chen, Yao ^{[4
]}

Zhang, Yihua ^{[2
]}

Fleck, Christian ^{[3
]}

机构：

[1] Southeast Univ, Jiangsu Prov Hitech Key Lab Biomed Res, Pharmaceut Res Ctr, Sch Chem & Chem Engn, Nanjing 211189, Jiangsu, Peoples R China

[2] China Pharmaceut Univ, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China

[3] Univ Jena, Inst Pharmacol & Toxicol, D-07743 Jena, Germany

[4] Univ Jena, Inst Pharm, Jena, Germany

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2014年 / 76卷

基金：

中国国家自然科学基金;

关键词：

Anti-Alzheimer; AChE inhibitors; Neuroprotective agents; A beta aggregation inhibitors; Galantamine analogs; POTENT ACETYLCHOLINESTERASE INHIBITORS; DISEASE; GALANTHAMINE; AGGREGATION; PEPTIDE; SCOPOLAMINE; CYCLIZATION; RATS;

D O I：

10.1016/j.ejmech.2014.02.035

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Facing the multifactorial nature of Alzheimer's disease, twelve dibenzofuran/carbazole derivatives, which can be considered as the D-ring opened analogs of galantamine, have been designed and synthesized as multifunctional anti-Alzheimer agents. In vitro tests revealed that compounds 3 and 5, which bear a nitrate moiety in the molecule, showed a potent inhibition activity towards AChE and compound 3 showed a good A beta 42 aggregation inhibitory activity. Moreover, 3 and 5 could also release a relative low concentration of NO in vitro and they did not show toxicity to neuronal cells, while exerted a neuroprotective effect against the A beta-induced toxicity. More importantly, compound 3 showed a significant spatial memory improving effect in vivo, and a good safety in the ex vivo toxicity study. (C) 2014 Elsevier Masson SAS. All rights reserved.

引用

页码：376 / 386

页数：11

共 30 条

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