Toward a Rational Design of Multitarget-Directed Antioxidants: Merging Memoquin and Lipoic Acid Molecular Frameworks

被引：63

作者：

Bolognesi, Maria Laura ^{[1
]}

Cavalli, Andrea ^{[1
,2
]}

Bergarmini, Christian ^{[3
]}

Fato, Romana ^{[3
]}

Lenaz, Giorgio ^{[3
]}

Rosini, Michela ^{[1
]}

Bartolini, Manuela ^{[1
]}

Andrisano, Vincenza ^{[1
]}

Melchiorre, Carlo ^{[1
]}

机构：

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

[2] Italian Inst Technol, Dept Drug Discovery & Dev, I-16163 Genoa, Italy

[3] Univ Bologna, Dept Biochem G Moruzzi, I-40126 Bologna, Italy

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 52卷 / 23期

关键词：

BETA-AMYLOID FIBRILS; OXIDATIVE STRESS; ALZHEIMERS-DISEASE; MITOCHONDRIAL; DYSFUNCTION; STRATEGY; LIGANDS;

D O I：

10.1021/jm901123n

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Novel multitargeted antioxidants 3-6 were designed by combining the antioxidant features, namely, a benzoquinone fragment and a lipoyl function, of two multifunctional lead candidates. They were then evaluated to determine their profile against Alzheimer's disease. They showed antioxidant activity, improved following enzymatic reduction, in mitochondria and T67 cell line. They also displayed a balanced inhibitory profile against amyloid-beta aggregation and acetylcholinesterase, emerging as promising molecules for neuroprotectant lead discovery.

引用

页码：7883 / 7886

页数：4

共 23 条

[1] MTDL Design Strategy in the Context of Alzheimer's Disease: From Lipocrine to Memoquin and Beyond [J].

Bolognesi, M. L. ;

Rosini, M. ;

Andrisano, V. ;

Bartolini, M. ;

Minarini, A. ;

Tumiatti, V. ;

Melchiorre, C. .

CURRENT PHARMACEUTICAL DESIGN, 2009, 15 (06) :601-613

[2] Novel class of quinone-bearing polyamines as multi-target-directed ligands to combat Alzheimer's disease [J].

Bolognesi, Maria Laura ;

Banzi, Rita ;

Bartolini, Manuela ;

Cavalli, Andrea ;

Tarozzi, Andrea ;

Andrisano, Vincenza ;

Minarini, Anna ;

Rosini, Michela ;

Tumiatti, Vincenzo ;

Bergamini, Christian ;

Fato, Romana ;

Lenaz, Giorgio ;

Hrelia, Patrizia ;

Cattaneo, Antonino ;

Recanatini, Maurizio ;

Melchiorre, Carlo .

JOURNAL OF MEDICINAL CHEMISTRY, 2007, 50 (20) :4882-4897

[3] Memoquin: A Multi-Target-Directed Ligand as an Innovative Therapeutic Opportunity for Alzheimer's Disease [J].

Bolognesi, Maria Laura ;

Cavalli, Andrea ;

Melchiorre, Carlo .

NEUROTHERAPEUTICS, 2009, 6 (01) :152-162

[4] Multi-target-directed ligands to combat neurodegenerative diseases [J].

Cavalli, Andrea ;

Bolognesi, Maria Laura ;

Minarini, Anna ;

Rosini, Michela ;

Tumiatti, Vincenzo ;

Recanatini, Maurizio ;

Melchiorre, Carlo .

JOURNAL OF MEDICINAL CHEMISTRY, 2008, 51 (03) :347-372

[5] A small molecule targeting the multifactorial nature of Alzheimer's disease [J].

Cavalli, Andrea ;

Bolognesi, Maria Laura ;

Capsoni, Simona ;

Andrisano, Vincenza ;

Bartolini, Manuela ;

Margotti, Elisa ;

Cattaneo, Antonino ;

Recanatini, Maurizio ;

Melchiorre, Carlo .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2007, 46 (20) :3689-3692

[6] Oxidative stress in the brain: Novel cellular targets that govern survival during neurodegenerative disease [J].

Chong, ZZ ;

Li, FQ ;

Maiese, K .

PROGRESS IN NEUROBIOLOGY, 2005, 75 (03) :207-246

[7] Oxidative stress triggers-the amyloidogenic pathway in human vascular smooth muscle cells [J].

Coma, Mireia ;

Guix, Francesc X. ;

Ill-Raga, Gerard ;

Uribesalgo, Iris ;

Alameda, Francesc ;

Valverde, Miguel A. ;

Munoz, Francisco J. .

NEUROBIOLOGY OF AGING, 2008, 29 (07) :969-980

[8] Congo red and protein aggregation in neurodegenerative diseases [J].

Frid, Petrea ;

Anisimov, Sergey V. ;

Popovic, Natalija .

BRAIN RESEARCH REVIEWS, 2007, 53 (01) :135-160

[9] Lipoic acid as a novel treatment for Alzheimer's disease and related dementias [J].

Holmquist, Lina ;

Stuchbury, Grant ;

Berbaum, Katrin ;

Muscat, Sonja ;

Young, Simon ;

Hager, Klaus ;

Engel, Juergen ;

Munch, Gerald .

PHARMACOLOGY & THERAPEUTICS, 2007, 113 (01) :154-164

[10] How to design multi-target drugs: target search options in cellular networks [J].

Korcsmaros, Tamas ;

Szalay, Mate S. ;

Csaba Boede ;

Kovacs, Istvan A. ;

Csermely, Peter .

EXPERT OPINION ON DRUG DISCOVERY, 2007, 2 (06) :799-808

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