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Chem Biol Drug Des ; 98(1): 175-181, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33963669

RESUMEN

While screening for natural product scaffolds as potential anti-Alzheimer's disease (AD), oxymatrine (OMT) was found to relieve symptoms of AD through diminishing death of neuronal cells caused by microglia-induced inflammation. In this study, 13 derivatives of OMT were synthesized and their neuroprotective effects were evaluated on Aß1-42 -induced PC12 cells using MTT method. In addition, the best neuroprotective potencies were obtained with compounds 4, 6e, and 6f, which were selected for evaluation of decrease in IL-1ß and TNF-α in Aß1-42 -treated PC12 cells. Collectively, these data reveal that derivatives 6e and 6f possess the best ability of diminish IL-1ß production and reverse cell damage in all compounds, which are possible to develop as therapeutic agents for AD.


Asunto(s)
Alcaloides/síntesis química , Enfermedad de Alzheimer/tratamiento farmacológico , Fármacos Neuroprotectores/síntesis química , Quinolizinas/síntesis química , Bibliotecas de Moléculas Pequeñas/síntesis química , Alcaloides/farmacología , Animales , Supervivencia Celular/efectos de los fármacos , Descubrimiento de Drogas , Humanos , Inflamación/metabolismo , Interleucina-1beta/metabolismo , Microglía/efectos de los fármacos , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Células PC12 , Quinolizinas/farmacología , Ratas , Bibliotecas de Moléculas Pequeñas/farmacología , Relación Estructura-Actividad , Factor de Necrosis Tumoral alfa/metabolismo
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