English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/129700
Share/Impact:
Statistics
logo share SHARE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:
Title

3-Amidocoumarins as Potential Multifunctional Agents Against Neurodegenerative Diseases

AuthorsJoão Matos, Maria; Rodríguez-Enríquez, Fernanda; Borges, Fernanda; Santana, Lourdes; Uriarte, Eugenio; Estrada, Martín ; Rodríguez-Franco, María Isabel ; Laguna, Reyes; Viña, Dolores
KeywordsCoumarin
Parkinson′s disease
Monoamine oxidase
Inhibitors
Neuroprotection
Issue Date23-Oct-2015
PublisherJohn Wiley & Sons
CitationChemMedChem 10 (12) : 2071–2079 (2015)
AbstractMonoamine oxidase (MAO) generates reactive oxygen species (ROS), which cause neuronal cell death, causing neurodegeneration. Agents that are able to concurrently inhibit MAO and scavenge free radicals represent promising multifunctional neuroprotective agents that could be used to delay or slow the progression of neurodegenerative diseases. In this work, variously substituted 3-amidocoumarins are described that exert neuroprotection in vitro against hydrogen peroxide in rat cortical neurons, as well as antioxidant activity in a 1,1-diphenyl-2-picrylhydrazyl (DPPH⋅) radical scavenging assay. Selective and reversible inhibitors of the MAO-B isoform were identified. Interestingly, in the case of the 3-benzamidocoumarins, substitution at position 4 with a hydroxy group abolishes MAO-B activity, but the compounds remain active in the neuroprotection model. Further evaluation of 3-heteroarylamide derivatives indicates that it is the nature of the heterocycle that determines the neuroprotective effects. Evaluation in a parallel artificial membrane permeability assay (PAMPA) highlighted the need to further improve the blood–brain barrier permeability of this compound class. However, the compounds described herein adhere to Lipinski′s rule of five, suggesting that this novel scaffold has desirable properties for the development of potential drug candidates.
Publisher version (URL)http://dx.doi.org/10.1002/cmdc.201500408
URIhttp://hdl.handle.net/10261/129700
DOI10.1002/cmdc.201500408
E-ISSN1860-7187
Appears in Collections:(IQM) Artículos
Files in This Item:
File Description SizeFormat 
3-Amidocoumarins as Potential Multifunctional.pdf344,14 kBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.