Multitarget compounds bearing tacrine- and donepezil-like structural and functional motifs for the potential treatment of Alzheimer's disease

被引：146

作者：

Ismaili, Lhassane ^{[1
]}

Refouvelet, Bernard ^{[1
]}

Benchekroun, Mohamed ^{[1
,7
]}

Brogi, Simone ^{[2
,3
]}

Brindisi, Margherita ^{[2
,3
]}

Gemma, Sandra ^{[2
,3
]}

Campiani, Giuseppe ^{[2
,3
]}

Filipic, Slavica ^{[4
]}

Agbaba, Danica ^{[4
]}

Esteban, Gerard ^{[5
]}

Unzeta, Mercedes ^{[5
]}

Nikolic, Katarina ^{[4
]}

Butini, Stefania ^{[2
,3
]}

Marco-Contelles, Jose ^{[6
]}

机构：

[1] Univ Bourgogne Franche Comte, Neurosci Integrat & Clin EA 481, Lab Chim Organ & Therapeut, CHRU Besancon,UFR SMP,Univ Franche Comte, 19 Rue Ambroise Pare, F-25000 Besancon, France

[2] Univ Siena, European Res Ctr Drug Discovery & Dev NatSynDrugs, Via A Moro, I-53100 Siena, Italy

[3] Univ Siena, Dept Biotechnol Chem & Pharm, Via A Moro, I-53100 Siena, Italy

[4] Univ Belgrade, Fac Pharm, Inst Pharmaceut Chem, Vojvode Stepe 450, Belgrade 11000, Serbia

[5] Univ Autonoma Barcelona, Fac Med, Inst Neurociencies, Dept Bioquim & Biol Mol, E-08193 Barcelona, Spain

[6] CSIC, IQOG, Med Chem Lab, C Juan de la Cierva 3, E-28006 Madrid, Spain

[7] CNRS, Ctr Rech Gif Sur Yvette, Inst Chim Subst Nat, UPR 2301, Ave Terrasse, F-91198 Gif Sur Yvette, France

来源：

PROGRESS IN NEUROBIOLOGY | 2017年 / 151卷

关键词：

Cholinesterases; Acetylcholinesterase; Butyrylcholinesterase; Alzheimer's disease; beta-Amyloid; Multi-target-directed ligand; Beta secretase; Monoamine oxidases; Reactive oxygen species; Nitric oxide; Histamine receptor; Serotonin receptors; ACTIVE-SITE GORGE; CHOLINESTERASE/MONOAMINE OXIDASE-INHIBITORS; BETA-AMYLOID AGGREGATION; TARGET-DIRECTED LIGANDS; INDUCED COGNITION IMPAIRMENT; COMBINED MOLECULAR-DYNAMICS; SIGMA(1) RECEPTOR AGONIST; STRUCTURE-BASED DESIGN; FERULIC ACID HYBRIDS; ACETYLCHOLINESTERASE INHIBITORS;

D O I：

10.1016/j.pneurobio.2015.12.003

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Alzheimer's disease is a multifactorial and fatal neurodegenerative disorder characterized by decline of cholinergic function, deregulation of other neurotransmitter systems, beta-amyloid fibril deposition, and beta-amyloid oligomers formation. Based on the involvement of a relevant number of biological systems in Alzheimer's disease progression, multitarget compounds may enable therapeutic efficacy. Accordingly, compounds possessing, besides anticholinergic activity and beta-amyloid aggregation inhibition properties, metal chelating and/or nitric oxide releasing properties with additional antioxidant capacity were developed. Other targets relevant to Alzheimer's disease have also been considered in the last years for producing multitarget compounds such as beta-secretase, monoamino oxidases, serotonin receptors and sigma 1 receptors. The purpose of this review will be to highlight recent reports on the development of multitarget compounds for Alzheimer's disease published within the last years focusing on multifunctional ligands characterized by tacrine-like and donepezil-like structures. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：4 / 34

页数：31

共 237 条

[1] Elaborate ligand-based modeling coupled with QSAR analysis and in silico screening reveal new potent acetylcholinesterase inhibitors [J].