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

Base de dados
Ano de publicação
Tipo de documento
Intervalo de ano de publicação
1.
Molecules ; 27(9)2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35566242

RESUMO

Inhibitors of epigenetic writers such as DNA methyltransferases (DNMTs) are attractive compounds for epigenetic drug and probe discovery. To advance epigenetic probes and drug discovery, chemical companies are developing focused libraries for epigenetic targets. Based on a knowledge-based approach, herein we report the identification of two quinazoline-based derivatives identified in focused libraries with sub-micromolar inhibition of DNMT1 (30 and 81 nM), more potent than S-adenosylhomocysteine. Also, both compounds had a low micromolar affinity of DNMT3A and did not inhibit DNMT3B. The enzymatic inhibitory activity of DNMT1 and DNMT3A was rationalized with molecular modeling. The quinazolines reported in this work are known to have low cell toxicity and be potent inhibitors of the epigenetic target G9a. Therefore, the quinazoline-based compounds presented are attractive not only as novel potent inhibitors of DNMTs but also as dual and selective epigenetic agents targeting two families of epigenetic writers.


Assuntos
Inibidores Enzimáticos , Quinazolinas , DNA , DNA (Citosina-5-)-Metiltransferases/metabolismo , Metilação de DNA , Metilases de Modificação do DNA/química , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Epigênese Genética , Quinazolinas/farmacologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA