Protection from neurodegeneration in the 6-hydroxydopamine (6-OHDA) model of Parkinson's with novel 1-hydroxypyridin-2-one metal chelatorsElectronic supplementary information (ESI) available: X-ray crystallographic data collection and structural refinement details for acid 9. CCDC 983801. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c4mt00326h

Protection from neurodegeneration in the 6-hydroxydopamine (6-OHDA) model of Parkinson's with novel 1-hydroxypyridin-2-one metal chelatorsElectronic supplementary information (ESI) available: X-ray crystallographic data collection and structural refinement details for acid 9. CCDC 983801. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c4mt00326h

Brain iron accumulation has been associated with inciting the generation of oxidative stress in a host of chronic neurological diseases, including Parkinson's disease. Using the catecholaminergic neurotoxin 6-hydroxydopamine to lesion cellular dopaminergic pathways as a model of Parkinson'...

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Main Authors: Workman, David G, Tsatsanis, Andrew, Lewis, Frank W, Boyle, John P, Mousadoust, Maryam, Hettiarachchi, Nishani T, Hunter, Michael, Peers, Chris S, Tétard, David, Duce, James A
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Language:eng
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Summary:Brain iron accumulation has been associated with inciting the generation of oxidative stress in a host of chronic neurological diseases, including Parkinson's disease. Using the catecholaminergic neurotoxin 6-hydroxydopamine to lesion cellular dopaminergic pathways as a model of Parkinson's disease in culture, a selection of 1-hydroxypyridin-2-one (1,2-HOPO) metal chelators were synthesized and their neuroprotective properties were compared to the 3-hydroxypyridin-4-one; deferiprone (3,4-HOPO; DFP). Protection against 6-OHDA and iron insult by the novel compounds 6 and 9 was comparable to DFP. Iron associated changes by 6-OHDA imply that the neuroprotective capacity of these compounds are due to chelation of the neuronal labile iron pool and the requirement of the iron binding moiety of compound 6 for efficacy supported this hypothesis. In conclusion, two novel 1,2-HOPO's and DFP have comparable neuroprotection against Parkinsonian-associated neurotoxins and supports the continued development of hydroxypyridinone compounds as a non-toxic therapeutic agent in the treatment of neurodegenerative disease. We report that novel 1-hydroxypyridin-2-ones show comparable neuroprotective results to deferiprone in a cell culture model of Parkinson's disease.
ISSN:1756-5901
1756-591X