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Titolo:
Protective activity of aromatic amines and imines against oxidative nerve cell death
Autore:
Moosmann, B; Skutella, T; Beyer, K; Behl, C;
Indirizzi:
Max Planck Inst Psychiat, D-80804 Munich, Germany Max Planck Inst Psychiat Munich Germany D-80804 D-80804 Munich, Germany Humboldt Univ, Charite, Neurosci Res Ctr, D-10118 Berlin, Germany HumboldtUniv Berlin Germany D-10118 ci Res Ctr, D-10118 Berlin, Germany Univ Munich, Inst Metab Biochem, D-80336 Munich, Germany Univ Munich Munich Germany D-80336 etab Biochem, D-80336 Munich, Germany
Titolo Testata:
BIOLOGICAL CHEMISTRY
fascicolo: 11, volume: 382, anno: 2001,
pagine: 1601 - 1612
SICI:
1431-6730(200111)382:11<1601:PAOAAA>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
AMYOTROPHIC-LATERAL-SCLEROSIS; BLOOD-BRAIN-BARRIER; ALZHEIMERS-DISEASE; ANTIOXIDANT ACTIVITY; REACTIVE OXYGEN; VITAMIN-E; PARKINSONS-DISEASE; ALPHA-TOCOPHEROL; CONTROLLED TRIAL; MOTOR-NEURONS;
Keywords:
antioxidant; cytoprotection; free radical; neurodegeneration; oxidative stress; quantitative structure-activity relationship (QSAR);
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
65
Recensione:
Indirizzi per estratti:
Indirizzo: Behl, C Max Planck Inst Psychiat, D-80804 Munich, Germany Max Planck Inst Psychiat Munich Germany D-80804 Munich, Germany
Citazione:
B. Moosmann et al., "Protective activity of aromatic amines and imines against oxidative nerve cell death", BIOL CHEM, 382(11), 2001, pp. 1601-1612

Abstract

Oxidative stress is a widespread phenomenon in the pathology of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Neuronal cell death due to oxidative stress may causally contribute to the pathogeneses of these diseases. Therefore, neuroprotective antioxidants are considered to be a promising approach to slow down disease progression. We have investigated different aromatic amine and imine compounds for neuroprotective antioxidant functions in cell culture, and found that these compounds possess excellent cytoprotective potential in diverse paradigms of oxidative neuronal cell death, including clonal celllines, primary cerebellar neurons, and organotypic hippocampal slice cultures. Aromatic amines and imines are effective against oxidative glutamate toxicity, glutathione depletion, and hydrogen peroxide toxicity. Their mode of action as direct antioxidants; was experimentally confirmed by electron spin resonance spectroscopy, cell-free brain lipid peroxidation assays, andintracellular peroxide measurements. With half-maximal effective concentrations of 20-75 nm in different neuroprotection experiments, the aromatic imines phenothiazine, phenoxazine, and iminostilbene proved to be about two orders of magnitude more effective than common phenolic antioxidants. This remarkable efficacy could be directly correlated to calculated properties ofthe compounds by means of a novel, quantitative structure-activity relationship model. We conclude that bridged bisarylimines with a single free NH-bond, such as iminostilbene, are superior neuroprotective antioxidants, and may be promising lead structures for rational drug development.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/04/20 alle ore 22:24:36