title: Microwave-assisted synthesis of hydroxyphenyl nitrones with protective action against oxidative stress.
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.
authors.affiliation: Grupo de Química Medicinal, Laboratorio de Química Orgánica, Facultad de Ciencias-Facultad de Química, Universidad de República, Iguá 4225, 11400 Montevideo, Uruguay.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Chavarría
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Perez
authors.forename: Concepción
authors.initials: C
authors.lastname: Pérez
authors.forename: Jose A
authors.initials: JA
authors.lastname: Morales Garcia
authors.forename: Sandra
authors.initials: S
authors.lastname: Alonso-Gil
authors.forename: Ana
authors.initials: A
authors.lastname: Pérez-Castillo
authors.forename: Carmen
authors.initials: C
authors.lastname: Gil
authors.forename: José M
authors.initials: JM
authors.lastname: Souza
authors.forename: Williams
authors.initials: W
authors.lastname: Porcal
mesh_terms: D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001812:Blood-Brain Barrier / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008872:Microwaves; D015394:Molecular Structure; D009447:Neuroblastoma / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D009589:Nitrogen Oxides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D016627:Oxidopamine; D030421:Peroxynitrous Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D018696:Neuroprotective Agents; D009589:Nitrogen Oxides; C015388:nitrones; D030421:Peroxynitrous Acid; D014443:Tyrosine; D016627:Oxidopamine