Microwave-assisted synthesis of hydroxyphenyl nitrones with protective action against oxidative stress

Chavarria, Cecilia; Perez, Daniel I.; Perez, Concepcion; Morales Garcia, Jose A.; Alonso-Gil, Sandra; Perez-Castillo, Ana; Gil, Carmen; Souza, Jose M.; Porcal, Williams

Abstract

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. (C) 2012 Elsevier Masson SAS. All rights reserved.

Más información

Título según WOS: ID WOS:000312745100005 Not found in local WOS DB
Título de la Revista: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volumen: 58
Editorial: ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
Fecha de publicación: 2012
Página de inicio: 44
Página final: 49
DOI:

10.1016/j.ejmech.2012.09.044

Notas: ISI