| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1394474 | European Journal of Medicinal Chemistry | 2012 | 6 Pages |
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.
Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Microwave-assisted synthesis gave good yield at short time. ► Neuroprotective properties of hydroxyphenyl nitrones were evaluated in neural cells. ► Nitrones avoided peroxynitrite dependent-protein nitration of alpha-synuclein. ► Hydroxyphenyl nitrones are promising therapeutic agents for neuroprotection.
