- Microwave-assisted synthesis of hydroxyphenyl nitrones with protective action against oxidative stress
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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.
- Chavarría, Cecilia,Perez, Daniel I.,Pérez, Concepción,Morales Garcia, Jose A.,Alonso-Gil, Sandra,Pérez-Castillo, Ana,Gil, Carmen,Souza, José M.,Porcal, Williams
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supporting information
p. 44 - 49
(2013/02/23)
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- COMPOSITIONS COMPRISING A NITRONE COMPOUND FOR USE IN TREATING UVEITIS
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Ophthalmic pharmaceutical compositions containing a pharmaceutically acceptable ophthalmic carrier and an inflammation-treating amount of a nitrone compound are disclosed. Also disclosed are methods for treating ocular inflammation conditions, such as uveitis, using pharmaceutical compositions.
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- Nitrogen inversion and N-O bond rotation processes in di- and tri-substituted hydroxylamines. A dynamic NMR study
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The barriers to inversion in several acyclic di- and tri-substituted hydroxylamines are determined by 1H NMR band shape analysis.The barriers range from 49.1 to 66.8 kJ mol1- and are discussed in terms of a conformational process which involves nitrogen inversion and rotation around the N-O bond.The N-benzyl group with an ortho hydroxy substituent increases the nitrogen inversion barrier by 10 kJ mol-1, which indicates the requirement of breaking of the intramolecular hydrogen bond prior to inversion.
- Ali, Sk. Asrof,Hassan, Azfar,Wazeer, Mohammed I. M.
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p. 1479 - 1484
(2007/10/03)
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- Rearrangement Reactions of Oxaziridines to Nitrones. X-Ray Crystal and Molecular Structure of N-t-Butyl-α(o-hydroxyphenyl)nitrone
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Substituted N-benzylidene-t-butylamines are oxidized with m-chloroperoxybenzoic acid to oxaziridines which can rearrange to the corresponding nitrones when electron-donating groups are present in the phenyl ring.The oxaziridine-to-nitrone rearrangement, which has been considered as a 'pseudo-abnormal' reaction, can also be catalysed by Lewis acids.It has been found that the rearrangement of 2-t-butyl-3-(o-hydroxyphenyl)oxaziridine to the corresponding nitrone is of first order.The rearrangement has been investigated for different substituents in the phenyl ring, andin the case of 2-t-butyl-3-phenyloxaziridine substituted in the ortho position with electron-donating groups it has been found that the presence of protons of a Lewis acid is necessary.An X-ray structure of α-(o-hydroxyphenyl)-N-t-butylnitrone shows strong hydrogen bonding between the nitrone oxygen and the hydrogen in the hydroxy group.The oxaziridine-to-nitrone rearrangement is also analysed from a theoretical point of view using ab initio calculations.A Mulliken-population analysis of the C-O and N-O bonds in the oxaziridine ring for para-substitued 2-t-butyl-3-phenyloxaziridines shows a reduction of the C-O bond population when an electron-donating group is present in the para position of the phenyl ring compared with an electron-withdrawing group; the N-O bond populations show the reverse picture.A state-correlation diagram for the oxaziridine-to-nitrone rearrangement is also presented and the experimental and theoretical results support each other.
- Christensen, Dorthe,Jorgensen, Karl Anker,Hazell, Rita G.
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p. 2391 - 2397
(2007/10/02)
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