The Antioxidant Additive Approach for Alzheimer's Disease Therapy: New Ferulic (Lipoic) Acid Plus Melatonin Modified Tacrines as Cholinesterases Inhibitors, Direct Antioxidants, and Nuclear Factor (Erythroid-Derived 2)-Like 2 Activators

被引：91

作者：

Benchekroun, Mohamed ^{[1
]}

Romero, Alejandro ^{[2
]}

Egea, Javier ^{[3
,4
]}

Leon, Rafael ^{[3
,4
]}

Michalska, Patrycja ^{[3
,4
]}

Buendia, Izaskun ^{[3
,4
]}

Jimeno, Maria Luisa ^{[5
]}

Jun, Daniel ^{[6
]}

Janockova, Jana ^{[7
]}

Sepsova, Vendula ^{[6
]}

Soukup, Ondrej ^{[7
]}

Bautista-Aguilera, Oscar M. ^{[1
]}

Refouvelet, Bernard ^{[1
]}

Ouari, Olivier ^{[8
]}

Marco-Contelles, Jose ^{[9
]}

Ismaili, Lhassane ^{[1
]}

机构：

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

[2] Univ Complutense Madrid, Fac Vet Med, Dept Toxicol & Pharmacol, E-28040 Madrid, Spain

[3] Hosp Univ La Princesa, Serv Farmacol Clin, Inst Invest Sanitaria, C Diego Leon 62, E-28006 Madrid, Spain

[4] Univ Autonoma Madrid, Fac Med, Inst I D Med Teofilo Hernando ITH, C Arzobispo Morcillo 4, E-28029 Madrid, Spain

[5] CSIC, Ctr Quim Organ Lora Tamayo CENQUIOR, C Juan Cierva 3, E-28006 Madrid, Spain

[6] Univ Def, Fac Mil Hlth Sci, Dept Toxicol & Mil Pharm, CZ-50001 Hradec Kralove, Czech Republic

[7] Univ Hosp Hradec Kralove, Biomed Res Ctr, CZ-50005 Hradec Kralove, Czech Republic

[8] Aix Marseille Univ, CNRS, ICR UMR 7273, F-13013 Marseille, France

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

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2016年 / 59卷 / 21期

关键词：

NEURODEGENERATIVE DISEASES; ACHE INHIBITORS; DRUG CANDIDATES; ACETYLCHOLINESTERASE; HYBRIDS; DERIVATIVES; DESIGN; HETERODIMERS; MECHANISMS; HYPOTHESIS;

D O I：

10.1021/acs.jmedchem.6b01178

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Novel multifunctional tacrines for Alzheimer's disease were obtained by Ugi-reaction between ferulic (or lipoic acid), a melatonin-like isocyanide, formaldehyde, and tacrine derivatives, according to the antioxidant additive approach in order to modulate the oxidative stress as therapeutic strategy. Compound 5c has been identified as a promising permeable agent showing excellent antioxidant properties, strong cholinesterase inhibitory activity, less hepatotoxicity than tacrine, and the best neuroprotective capacity, being able to significantly activate the Nrf2 transcriptional pathway.

引用

页码：9967 / 9973

页数：7

共 40 条

[1] THE CHOLINERGIC HYPOTHESIS OF GERIATRIC MEMORY DYSFUNCTION [J].

BARTUS, RT ;

DEAN, RL ;

BEER, B ;

LIPPA, AS .

SCIENCE, 1982, 217 (4558) :408-417

[2] Novel Tacrine-Grafted Ugi Adducts as Multipotent Anti-Alzheimer Drugs: A Synthetic Renewal in Tacrine-Ferulic Acid Hybrids [J].

Benchekroun, Mohamed ;

Bartolini, Manuela ;

Egea, Javier ;

Romero, Alejandro ;

Soriano, Elena ;

Pudlo, Marc ;

Luzet, Vincent ;

Andrisano, Vincenza ;

Jimeno, Maria-Luisa ;

Lopez, Manuela G. ;

Wehle, Sarah ;

Gharbi, Tijani ;

Refouvelet, Bernard ;

de Andres, Lucia ;

Herrera-Arozamena, Clara ;

Monti, Barbara ;

Bolognesi, Maria Laura ;

Isabel Rodriguez-Franco, Maria ;

Decker, Michael ;

Marco-Contelles, Jose ;

Ismaili, Lhassane .

CHEMMEDCHEM, 2015, 10 (03) :523-539

[3] ANALOGS OF 9-AMINO-1,2,3,4-TETRAHYDROACRIDINE [J].

BIELAVSKY, J .

COLLECTION OF CZECHOSLOVAK CHEMICAL COMMUNICATIONS, 1977, 42 (09) :2802-2808

[4] Multi-target-directed drug design strategy: From a dual binding site acetylcholinesterase inhibitor to a trifunctional compound against Alzheimer's disease [J].

Bolognesi, Maria Laura ;

Cavalli, Andrea ;

Valgimigli, Luca ;

Bartolini, Manuela ;

Rosini, Michela ;

Andrisano, Vincenza ;

Recanatini, Maurizio ;

Melchiorre, Carlo .

JOURNAL OF MEDICINAL CHEMISTRY, 2007, 50 (26) :6446-6449

[5] New melatonin-cinnamate hybrids as multi-target drugs for neurodegenerative diseases: Nrf2-induction, antioxidant effect and neuroprotection [J].

Buendia, Izaskun ;

Navarro, Elisa ;

Michalska, Patrycja ;

Gameiro, Isabel ;

Egea, Javier ;

Abril, Sheila ;

Lopez, Alicia ;

Gonzalez-Lafuente, Laura ;

Lopez, Manuela G. ;

Leon, Rafael .

FUTURE MEDICINAL CHEMISTRY, 2015, 7 (15) :1961-1969

[6] Evaluation of short-tether bis-THA AChE inhibitors. A further test of the dual binding site hypothesis [J].

Carlier, PR ;

Han, YF ;

Chow, ESH ;

Li, CPL ;

Wang, H ;

Lieu, TX ;

Wong, HS ;

Pang, YP .

BIOORGANIC & MEDICINAL CHEMISTRY, 1999, 7 (02) :351-357

[7] Dehydration of formamides using the Burgess Reagent: a new route to isocyanides [J].

Creedon, SM ;

Crowley, HK ;

McCarthy, DG .

JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1998, (06) :1015-1017

[8] Extending applicability of the oxygen radical absorbance capacity (ORAC-fluorescein) assay [J].

Dávalos, A ;

Gómez-Cordovés, C ;

Bartolomé, B .

JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 2004, 52 (01) :48-54

[9]

delGiudice MR, 1996, FARMACO, V51, P693

[10] A NEW AND RAPID COLORIMETRIC DETERMINATION OF ACETYLCHOLINESTERASE ACTIVITY [J].

ELLMAN, GL ;

COURTNEY, KD ;

ANDRES, V ;

FEATHERSTONE, RM .

BIOCHEMICAL PHARMACOLOGY, 1961, 7 (02) :88-&

← 1 2 3 4 →