Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Más filtros

Banco de datos
Tipo del documento
País de afiliación
Intervalo de año de publicación
1.
Chem Pharm Bull (Tokyo) ; 65(1): 56-65, 2017 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-27746410

RESUMEN

Oxidative stress plays a crucial role in neurological diseases, resulting in excessive production of reactive oxygen species, mitochondrial dysfunction and cell death. In this work, we designed and synthesized a series of tetramethylpyrazine (TMP) derivatives and investigated their abilities for scavenging free radicals and preventing against oxidative stress-induced neuronal damage in vitro. Among them, compound 22a, consisted of TMP, caffeic acid and a nitrone group, showed potent radical-scavenging activity. Compound 22a had broad neuroprotective effects, including rescuing iodoacetic acid-induced neuronal loss, preventing from tert-butylhydroperoxide (t-BHP)-induced neuronal injury. Compound 22a exerted its neuroprotective effect against t-BHP injury via activation of the phosphatidyl inositol 3-kinase (PI3K)/Akt signaling pathway. Furthermore, in a rat model of permanent middle cerebral artery occlusion, compound 22a significantly improved neurological deficits, and alleviated the infarct area and brain edema. In conclusion, our results suggest that compound 22a could be a potential neuroprotective agent for the treatment of neurological disease, particularly ischemic stroke.


Asunto(s)
Arteriopatías Oclusivas/tratamiento farmacológico , Diseño de Fármacos , Depuradores de Radicales Libres/farmacología , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Pirazinas/farmacología , Animales , Apoptosis/efectos de los fármacos , Arteriopatías Oclusivas/patología , Muerte Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Depuradores de Radicales Libres/síntesis química , Depuradores de Radicales Libres/química , Estructura Molecular , Neuronas/patología , Fármacos Neuroprotectores/síntesis química , Fármacos Neuroprotectores/química , Estrés Oxidativo/efectos de los fármacos , Células PC12 , Pirazinas/síntesis química , Pirazinas/química , Ratas , terc-Butilhidroperóxido/antagonistas & inhibidores , terc-Butilhidroperóxido/farmacología
2.
J Mol Neurosci ; 56(4): 977-987, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25982925

RESUMEN

Neurodegenerative disorders are one of the leading causes of death among the elderly. Therapeutic approaches with a single target have proven unsuccessful in treating these diseases. Structural combination of multi-functional compounds may lead to a molecule with multiple properties. In this study, we designed and synthesized T-006, a novel analog derived from two multi-functional neuroprotective chemicals, tetramethylpyrazine and J147. The methoxyphenyl group of J147 was replaced by tetramethylpyrazine. Bioactivity evaluation showed that T-006 at very low concentrations had multi-functional neuroprotective effects including rescuing iodoacetic acid-induced neuronal loss, preventing oxidative stress-induced neurotoxicity and reducing glutamate-induced excitotoxicity in vitro. Most importantly, T-006 significantly ameliorated memory impairments in APP/PS1 transgenic mice. These multiple functions of a single molecule suggest that T-006 is a promising novel neuroprotective agent for treating various neurodegenerative disorders, including and in particular Alzheimer's disease.


Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Antioxidantes/farmacología , Hidrazonas/farmacología , Fármacos Neuroprotectores/farmacología , Pirazinas/farmacología , Animales , Antioxidantes/síntesis química , Antioxidantes/uso terapéutico , Células Cultivadas , Hidrazonas/síntesis química , Ratones , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Fármacos Neuroprotectores/síntesis química , Fármacos Neuroprotectores/uso terapéutico , Células PC12 , Pirazinas/síntesis química , Pirazinas/química , Ratas , Ratas Sprague-Dawley
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA