alpha-Aryl-N-aryl nitrones: Synthesis and screening of a new scaffold for cellular protection against an oxidative toxic stimulus

Autor(es)

Matias, A. C. ^[1] ; Biazolla, G. ^[1] ; Cerchiaro, G. ^[1] ; Keppler, A. F. ^[1]

Afiliação do(s) autor(es)

^[1] Fed Univ ABC CCNH, UFABC, Ctr Nat Sci & Humanities, BR-09210580 Santo Andre, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Bioorganic & Medicinal Chemistry; v. 24, n. 2, p. 232-239, JAN 15 2016.
• Citações Web of Science: 4

Resumo

Nitrone-containing compounds are commonly employed as spin traps of free radical species in chemical and biological studies. Some molecules as alpha-phenyl-N-t-butyl nitrone (PBN) and its derivatives have been tested as potential drugs to treat oxidative stress related diseases, as Alzheimer and stroke for example. In this work we report the design and the synthesis of alpha-aryl-N-aryl nitrones and their cytoprotection profile on human neuroblastoma cells (SH-SY5Y) under induced oxidative stress. All the nine synthesized nitrones showed a significant response at low micromolar concentration. The selected compound 8 (alpha-phenyl-N-phenyl nitrone) increased the reduced glutathione (GSH) levels by 65% and lowered the necrotic cell death from 25.8% to 3.8%. Based on our data, the designed highly conjugated nitrone double-bond skeleton can be considered as a good scaffold for further studies regarding oxidative stress-related diseases. (c) 2015 Elsevier Ltd. All rights reserved. (AU)

• Processo FAPESP: 12/01397-9 - Efeitos da expressão da metaloenzima superóxido dismutase na regulação da geração de espécies reativas de oxigênio em células de mamíferos em cultura e em neurônios motores
• Beneficiário: Giselle Cerchiaro
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/07717-5 - Nitronas e hidroxilaminas com potencial farmacológico: síntese, prospecção da atividade antioxidante e estudos celulares
• Beneficiário: Artur Franz Keppler
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 14/15534-3 - Síntese de nitronas com potencial farmacológico
• Beneficiário: Giovanna Biazolla
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica