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Chem Biol Drug Des ; 98(1): 175-181, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33963669

RESUMO

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.


Assuntos
Alcaloides/síntese química , Doença de Alzheimer/tratamento farmacológico , Fármacos Neuroprotetores/síntese química , Quinolizinas/síntese química , Bibliotecas de Moléculas Pequenas/síntese química , Alcaloides/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Descoberta de Drogas , Humanos , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Microglia/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Células PC12 , Quinolizinas/farmacologia , Ratos , Bibliotecas de Moléculas Pequenas/farmacologia , Relação Estrutura-Atividade , Fator de Necrose Tumoral alfa/metabolismo
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