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Protective activity of aromatic amines and imines against oxidative nerve cell death.
Biol Chem. 2001 Nov; 382(11):1601-12.BC

Abstract

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.

Authors+Show Affiliations

Max-Planck-Institute of Psychiatry, Munich, Germany.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11767950

Citation

Moosmann, B, et al. "Protective Activity of Aromatic Amines and Imines Against Oxidative Nerve Cell Death." Biological Chemistry, vol. 382, no. 11, 2001, pp. 1601-12.
Moosmann B, Skutella T, Beyer K, et al. Protective activity of aromatic amines and imines against oxidative nerve cell death. Biol Chem. 2001;382(11):1601-12.
Moosmann, B., Skutella, T., Beyer, K., & Behl, C. (2001). Protective activity of aromatic amines and imines against oxidative nerve cell death. Biological Chemistry, 382(11), 1601-12.
Moosmann B, et al. Protective Activity of Aromatic Amines and Imines Against Oxidative Nerve Cell Death. Biol Chem. 2001;382(11):1601-12. PubMed PMID: 11767950.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protective activity of aromatic amines and imines against oxidative nerve cell death. AU - Moosmann,B, AU - Skutella,T, AU - Beyer,K, AU - Behl,C, PY - 2002/1/5/pubmed PY - 2002/5/25/medline PY - 2002/1/5/entrez SP - 1601 EP - 12 JF - Biological chemistry JO - Biol Chem VL - 382 IS - 11 N2 - 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. SN - 1431-6730 UR - https://www.unboundmedicine.com/medline/citation/11767950/Protective_activity_of_aromatic_amines_and_imines_against_oxidative_nerve_cell_death_ L2 - https://www.degruyter.com/document/doi/10.1515/BC.2001.195 DB - PRIME DP - Unbound Medicine ER -