抑制乙酰胆碱酯酶、β-淀粉样蛋白聚集以及阿尔茨海默病中的N-甲基-D-天冬氨酸受体：多靶点导向配体热潮的一个有前景的方向。

Inhibition of acetylcholinesterase, beta-amyloid aggregation, and NMDA receptors in Alzheimer's disease: a promising direction for the multi-target-directed ligands gold rush.

作者信息

Rosini Michela, Simoni Elena, Bartolini Manuela, Cavalli Andrea, Ceccarini Luisa, Pascu Nicoleta, McClymont David W, Tarozzi Andrea, Bolognesi Maria L, Minarini Anna, Tumiatti Vincenzo, Andrisano Vincenza, Mellor Ian R, Melchiorre Carlo

机构信息

Department of Pharmaceutical Sciences, Alma Mater Studiorum, UniVersity of Bologna, Via Belmeloro 6, I-40126 Bologna, Italy.

出版信息

J Med Chem. 2008 Aug 14;51(15):4381-4. doi: 10.1021/jm800577j. Epub 2008 Jul 8.

DOI:10.1021/jm800577j

PMID:18605718

Abstract

Alzheimer's disease (AD) is a multifactorial syndrome with several target proteins contributing to its etiology. To confront AD, an innovative strategy is to design single chemical entities able to simultaneously modulate more than one target. Here, we present compounds that inhibit acetylcholinesterase and NMDA receptor activity. Furthermore, these compounds inhibit AChE-induced Abeta aggregation and display antioxidant properties, emerging as lead candidates for treating AD.

摘要

阿尔茨海默病（AD）是一种多因素综合征，有多种靶蛋白参与其病因。为应对AD，一种创新策略是设计能够同时调节多个靶点的单一化学实体。在此，我们展示了抑制乙酰胆碱酯酶和NMDA受体活性的化合物。此外，这些化合物抑制AChE诱导的Aβ聚集并具有抗氧化特性，有望成为治疗AD的先导候选药物。