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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2001-12-20
pubmed:abstractText
Oxidative stress is a widespread phenomenon in the pathology of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Neuronal cell death due to oxidative stress may causally contribute to the pathogeneses of these diseases. Therefore, neuroprotective antioxidants are considered to be a promising approach to slow down disease progression. We have investigated different aromatic amine and imine compounds for neuroprotective antioxidant functions in cell culture, and found that these compounds possess excellent cytoprotective potential in diverse paradigms of oxidative neuronal cell death, including clonal cell lines, primary cerebellar neurons, and organotypic hippocampal slice cultures. Aromatic amines and imines are effective against oxidative glutamate toxicity, glutathione depletion, and hydrogen peroxide toxicity. Their mode of action as direct antioxidants was experimentally confirmed by electron spin resonance spectroscopy, cell-free brain lipid peroxidation assays, and intracellular peroxide measurements. With half-maximal effective concentrations of 20-75 nM in different neuroprotection experiments, the aromatic imines phenothiazine, phenoxazine, and iminostilbene proved to be about two orders of magnitude more effective than common phenolic antioxidants. This remarkable efficacy could be directly correlated to calculated properties of the compounds by means of a novel, quantitative structure-activity relationship model. We conclude that bridged bisarylimines with a single free NH-bond, such as iminostilbene, are superior neuroprotective antioxidants, and may be promising lead structures for rational drug development.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1431-6730
pubmed:author
pubmed:issnType
Print
pubmed:volume
382
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1601-12
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed-meshheading:11767950-Amines, pubmed-meshheading:11767950-Animals, pubmed-meshheading:11767950-Animals, Newborn, pubmed-meshheading:11767950-Cell Death, pubmed-meshheading:11767950-Cell Survival, pubmed-meshheading:11767950-Dibenzazepines, pubmed-meshheading:11767950-Electron Spin Resonance Spectroscopy, pubmed-meshheading:11767950-Hippocampus, pubmed-meshheading:11767950-Humans, pubmed-meshheading:11767950-Hydrogen Bonding, pubmed-meshheading:11767950-Imines, pubmed-meshheading:11767950-Lipid Peroxidation, pubmed-meshheading:11767950-Mice, pubmed-meshheading:11767950-Neurons, pubmed-meshheading:11767950-Nitrogen, pubmed-meshheading:11767950-Organ Culture Techniques, pubmed-meshheading:11767950-Oxidative Stress, pubmed-meshheading:11767950-Peroxides, pubmed-meshheading:11767950-Rats, pubmed-meshheading:11767950-Rats, Sprague-Dawley, pubmed-meshheading:11767950-Solvents, pubmed-meshheading:11767950-Structure-Activity Relationship
pubmed:year
2001
pubmed:articleTitle
Protective activity of aromatic amines and imines against oxidative nerve cell death.
pubmed:affiliation
Max-Planck-Institute of Psychiatry, Munich, Germany.
pubmed:publicationType
Journal Article