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1.
Org Biomol Chem ; 9(8): 2602-5, 2011 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-21403943

RESUMO

Flexible protected 1,3,4-trihydroxy-2-butanone is synthesized in high enantiomeric excesses by using asymmetric homo- and cross- acyloin coupling of aliphatic aldehydes catalyzed by benzaldehyde lyase.


Assuntos
Acetaldeído/análogos & derivados , Acetaldeído/metabolismo , Aldeído Liases/metabolismo , Biocatálise , Estrutura Molecular , Estereoisomerismo , Especificidade por Substrato
2.
Chem Biol Drug Des ; 73(3): 355-64, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19207472

RESUMO

Spinal muscular atrophy is an autosomal recessive motor neuron disease that is caused by mutation of the survival motor neuron gene (SMN1) but all patients retain a nearly identical copy, SMN2. The disease severity correlates inversely with increased SMN2 copy. Currently, the most promising therapeutic strategy for spinal muscular atrophy is induction of SMN2 gene expression by histone deacetylase inhibitors. Polyphenols are known for protection against oxidative stress and degenerative diseases. Among our candidate prodrug library, we found that (E )-resveratrol, which is one of the polyphenolic compounds, inhibited histone deacetylase activity in a concentration-dependent manner and half-maximum inhibition was observed at 650 microM. Molecular docking studies showed that (E )-resveratrol had more favorable free energy of binding (-9.09 kcal/mol) and inhibition constant values (0.219 microM) than known inhibitors. To evaluate the effect of (E )-resveratrol on SMN2 expression, spinal muscular atrophy type I fibroblast cell lines was treated with (E )-resveratrol. The level of full-length SMN2 mRNA and protein showed 1.2- to 1.3-fold increase after treatment with 100 microM (E )-resveratrol in only one cell line. These results indicate that response to (E )-resveratrol treatment is variable among cell lines. This data demonstrate a novel activity of (E )-resveratrol and that it could be a promising candidate for the treatment of spinal muscular atrophy.


Assuntos
Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Inibidores de Histona Desacetilases , Atrofia Muscular Espinal/tratamento farmacológico , Estilbenos/química , Estilbenos/farmacologia , Linhagem Celular , Simulação por Computador , Inibidores Enzimáticos/uso terapêutico , Fibroblastos/efeitos dos fármacos , Histona Desacetilases/metabolismo , Humanos , Atrofia Muscular Espinal/genética , Resveratrol , Proteínas do Complexo SMN/genética , Proteínas do Complexo SMN/metabolismo , Estilbenos/uso terapêutico , Relação Estrutura-Atividade , Proteína 2 de Sobrevivência do Neurônio Motor , Termodinâmica
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