Synthesis and Evaluation of 3-(furo[2,3-b]pyridin-3-yl)-4-(1H-indol-3-yl)-maleimides as Novel GSK-3ß Inhibitors and Anti-Ischemic Agents.
Chem Biol Drug Des
; 86(4): 746-52, 2015 Oct.
Article
em En
| MEDLINE
| ID: mdl-25711384
ABSTRACT
A series of novel 3-(furo[2,3-b]pyridin-3-yl)-4-(1H-indol-3-yl)-maleimides were designed, synthesized, and biologically evaluated for their GSK-3ß inhibitory activities. Most compounds showed favorable inhibitory activities against GSK-3ß protein. Among them, compounds 5n, 5o, and 5p significantly reduced GSK-3ß substrate tau phosphorylation at Ser396 in primary neurons, indicating inhibition of cellular GSK-3ß activity. In the in vitro neuronal injury models, compounds 5n, 5o, and 5p prevented neuronal death against glutamate, oxygen-glucose deprivation, and nutrient serum deprivation which are closely associated with cerebral ischemic stroke. In the in vivo cerebral ischemia animal model, compound 5o reduced infarct size by 10% and improved the neurological deficit. The results may provide new insights into the development of novel GSK-3ß inhibitors with potential neuroprotective activity against brain ischemic stroke.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Isquemia Encefálica
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Fármacos Neuroprotetores
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Quinase 3 da Glicogênio Sintase
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Inibidores Enzimáticos
Limite:
Animals
Idioma:
En
Revista:
Chem Biol Drug Des
Assunto da revista:
BIOQUIMICA
/
FARMACIA
/
FARMACOLOGIA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
China