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Eur J Med Chem ; 58: 44-9, 2012 Dec.
Article de Anglais | MEDLINE | ID: mdl-23085773

RÉSUMÉ

Oxidative stress plays an important role in neuronal death in neurodegenerative disorders such as Parkinson's disease (PD). Hydroxyphenyl nitrones, derivatives of the nitrone spin trap alpha-phenyl-N-tert-butylnitrone (PBN), were synthesized and their antioxidant, anti-inflammatory and neuroprotective activity in neural cells evaluated. These hydroxyphenyl nitrones 5-7 were synthesized by reaction of the corresponding hydroxybenzaldehyde with N-tert-butyl hydroxylamine under microwave irradiation. They showed good peroxyl free radical scavenger capacities, analyzed by oxygen radical absorbance capacity (ORAC). Also inhibited peroxynitrite-mediated tyrosine nitration of alpha-synuclein in vitro and protected human neuroblastoma (SH-SY5Y) cells against SIN-1 and 6-OHDA toxicity when micromolar concentrations were used. Besides, the hydroxyphenyl nitrones evaluated showed anti-inflammatory activity modulating nitrite production in primary neural cell cultures of astrocytes and microglia treated with lipopolysaccharide (LPS), a potent inflammatory agent. These experimental data suggest a potential therapeutic use of these hydroxyphenyl nitrones against oxygen and nitrogen reactive species involved in neurodegenerative pathology.


Sujet(s)
Anti-inflammatoires/pharmacologie , Antioxydants/pharmacologie , Micro-ondes , Neuroprotecteurs/pharmacologie , Oxydes d'azote/pharmacologie , Stress oxydatif/effets des médicaments et des substances chimiques , Anti-inflammatoires/synthèse chimique , Anti-inflammatoires/composition chimique , Antioxydants/synthèse chimique , Antioxydants/composition chimique , Barrière hémato-encéphalique/effets des médicaments et des substances chimiques , Survie cellulaire/effets des médicaments et des substances chimiques , Relation dose-effet des médicaments , Humains , Structure moléculaire , Neuroblastome/induit chimiquement , Neuroblastome/anatomopathologie , Neuroblastome/prévention et contrôle , Neuroprotecteurs/synthèse chimique , Neuroprotecteurs/composition chimique , Oxydes d'azote/synthèse chimique , Oxydes d'azote/composition chimique , Oxidopamine , Acide peroxynitreux/antagonistes et inhibiteurs , Acide peroxynitreux/pharmacologie , Relation structure-activité , Tyrosine/antagonistes et inhibiteurs , Tyrosine/métabolisme
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