Design, synthesis, and biological evaluation of some novel 4-aminoquinazolines as Pan-PI3K inhibitors.
Bioorg Med Chem
; 27(13): 2729-2740, 2019 07 01.
Article
em En
| MEDLINE
| ID: mdl-31097403
ABSTRACT
A series of 4-aminoquinazolines derivatives containing hydrophilic group were designed and identified as potent Pan-PI3K inhibitors in this study. The results of antiproliferative assays in vitro showed that this series of compounds had strong inhibition of tumor growth, especially compound 7b for MCF-7 cells but weak inhibition to normal cells. PI3K kinase assay showed that 7b had high activity for three PI3K isoforms with the IC50 values of picomole. The western blot assay indicated that 7b could decrease the phospho-Akt (S473) in a dose-dependent manner. Further experiments showed that 7b could induce apoptosis in MCF-7 cells. Four key hydrogen bonding interactions were found in the docking of 7b with PI3K kinase. All these results suggested that 7b is a potent PI3K inhibitor and could be considered as a potential candidate for the development of anticancer agents.
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Base de dados:
MEDLINE
Assunto principal:
Quinazolinas
/
Fosfatidilinositol 3-Quinases
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Inibidores de Proteínas Quinases
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article