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Title

α-aryl-N-alkyl nitrones, as potential agents for stroke treatment: Synthesis, theoretical calculations, antioxidant, anti-inflammatory, neuroprotective, and brain-blood barrier permeability properties

AuthorsChioua, Mourad ; Sucunza, D.; Soriano, Elena ; Hadjipavlou-Litina, Dimitra; Alcázar González, Alberto; Ayuso, I.; Oset-Gasque, María J.; Gonzalez, M. P.; Monjas, Leticia ; Rodríguez-Franco, María Isabel ; Marco-Contelles, José ; Marco-Contelles, José ; Samadi, Abdelouahid
Issue Date2015
PublisherAmerican Chemical Society
CitationJournal of Medicinal Chemistry 55: 153-168 (2015)
AbstractWe report the synthesis, theoretical calculations, the antioxidant, anti-inflammatory, and neuroprotective properties, and the ability to cross the blood-brain barrier (BBB) of (Z)-α-aryl and heteroaryl-N-alkyl nitrones as potential agents for stroke treatment. The majority of nitrones compete with DMSO for hydroxyl radicals, and most of them are potent lipoxygenase inhibitors. Cell viability-related (MTT assay) studies clearly showed that nitrones 1-3 and 10 give rise to significant neuroprotection. When compounds 1-11 were tested for necrotic cell death (LDH release test) nitrones 1-3, 6, 7, and 9 proved to be neuroprotective agents. In vitro evaluation of the BBB penetration of selected nitrones 1, 2, 10, and 11 using the PAMPA-BBB assay showed that all of them cross the BBB. Permeable quinoline nitrones 2 and 3 show potent combined antioxidant and neuroprotective properties and, therefore, can be considered as new lead compounds for further development in specific tests for potential stroke treatment. © 2011 American Chemical Society.
URIhttp://hdl.handle.net/10261/121674
DOI10.1021/jm201105a
Identifiersdoi: 10.1021/jm201105a
issn: 0022-2623
e-issn: 1520-4804
Appears in Collections:(IQM) Artículos
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