3-Amidocoumarins as Potential Multifunctional Agents against Neurodegenerative Diseases

• Tipo: Artigo em Revista Científica Internacional
• Data: 2015

Autores

Matos, MJ (Autor) Outra; Rodriguez Enriquez, F (Autor) Outra; Fernanda Borges (Autor) FCUP; Santana, L (Autor) Outra; Uriarte, E (Autor) Outra; Estrada, M (Autor) Outra; Isabel Rodriguez Franco, MI (Autor) Outra; Laguna, R (Autor) Outra; Vina, D (Autor) Outra

Revista

Título: ChemMedChem

Vol. 10

Páginas: 2071-2079

ISSN: 1860-7179

Editora: Wiley-Blackwell

Indexação

ISI Web of Knowledge - 23 Citações

Scopus - 25 Citações

Outras Informações

ID Authenticus: P-00J-YX9

DOI: 10.1002/cmdc.201500408

Abstract (EN): Monoamine 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 position4 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 Lipinskis rule of five, suggesting that this novel scaffold has desirable properties for the development of potential drug candidates.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 9