Bis(7)-tacrine Derivatives as Multitarget-Directed Ligands: Focus on Anticholinesterase and Antiamyloid Activities

被引：54

作者：

Bolognesi, Maria Laura ^{[1
]}

Bartolini, Manuela ^{[1
]}

Mancini, Francesca ^{[1
]}

Chiriano, Gianpaolo ^{[1
]}

Ceccarini, Luisa ^{[1
]}

Rosini, Michela ^{[1
]}

Milelli, Andrea ^{[1
]}

Tumiatti, Vincenzo ^{[1
]}

Andrisano, Vincenza ^{[1
]}

Melchiorre, Carlo ^{[1
]}

机构：

[1] Univ Bologna, Dipartimento Sci Farmaceut, I-40126 Bologna, Italy

来源：

CHEMMEDCHEM | 2010年 / 5卷 / 08期

关键词：

acetylcholinesterases; Alzheimer's disease; amyloid-beta peptides; beta-secretases; butyrylcholinesterase; drug design; ANTI-ALZHEIMER COMPOUNDS; ACETYLCHOLINESTERASE INHIBITORS; AMYLOID AGGREGATION; BETA-SECRETASE; DISEASE; TARGETS; BINDING; BACE-1; DRUGS; SITE;

D O I：

10.1002/cmdc.201000086

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：

(Figure Presented) Multitarget drug discovery is an emerging approach to the design of new drugs to treat Alzheimer's disease. Using this strategy, we developed a series of dimeric ligands derived from the lead candidate bis(7)-tacrine (1), for which a multifunctional profile has been disclosed. These derivatives were evaluated at validated targets, namely cholinesterases and amyloid production and aggregation. Compound 3 resulted more effective than 1 in inhibiting BACE-1 activity and amyloid self-aggregation. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.

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收藏

页码：1215 / 1220

页数：6

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