Structure-activity relationships of memoquin: Influence of the chain chirality in the multi-target mechanism of action

被引：24

作者：

Bolognesi, Maria Laura ^{[1
]}

Bartolini, Manuela ^{[1
]}

Rosini, Michela ^{[1
]}

Andrisano, Vincenza ^{[1
]}

Melchiorre, Carlo ^{[1
]}

机构：

[1] Alma Mater Studiorum Bologna Univ, Dept Pharmaceut Sci, I-40126 Bologna, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 15期

关键词：

Alzheimer's disease; Acetylcholinesterase; Butyrylcholinesterase; Amyloid-beta; Small molecule protein-protein interaction inhibitors; TARGET-DIRECTED LIGANDS; SITE ACETYLCHOLINESTERASE INHIBITORS; AMYLOID-BETA AGGREGATION; ALZHEIMERS-DISEASE; POLYAMINES; DESIGN;

D O I：

10.1016/j.bmcl.2009.05.087

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

The present article expands on the study of structure-activity relationships of the novel class of quinone-bearing polyamines, as multi-target-directed ligands against Alzheimer's disease. Namely, the effect of inserting a methyl substituent at the alpha position of the terminal benzyl amine moieties of lead candidate 1 (memoquin) was evaluated at the multiple targets involved in the multifunctional mechanism of action. The RR stereoisomer 2 resulted more effective than 1 in reverting two important effects mediated by acetylcholinesterase (AChE), that is, acetylcholine hydrolysis and AChE-induced amyloid-beta aggregation. (C) 2009 Elsevier Ltd. All rights reserved.

引用

收藏

页码：4312 / 4315

页数：4

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