Styryl Quinazolinones as Potential Inducers of Myeloid Differentiation via Upregulation of C/EBPα.
Molecules
; 23(8)2018 Aug 03.
Article
em En
| MEDLINE
| ID: mdl-30081475
ABSTRACT
The CCAAT enhancer-binding protein α (C/EBPα) plays an important role in myeloid cell differentiation and in the enhancement of C/EBPα expression/activity, which can lead to granulocytic differentiation in acute myeloid leukemia (AML) cells. We found that styryl quinazolinones induce upregulation of C/EBPα expression, and thereby induce myeloid differentiation in human myeloid leukemia cell lines. We screened a series of active styryl quinazolinones and evaluated the structureâ»activity relationship (SAR) of these small molecules in inducing C/EBPα expression-thereby prompting the leukemic cells to differentiate. We observed that compound 78 causes differentiation at 3 µM concentration, while 1 induces differentiation at 10 µM concentration. We also observed an increase in the expression of neutrophil differentiation marker CD11b upon treatment with 78. Both the C/EBPα and C/EBPε levels were found to be upregulated by treatment with 78. These SAR findings are inspiration to develop further modified styryl quinazolinones, in the path of this novel differentiation therapy, which can contribute to the care of patients with AML.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Estirenos
/
Proteína alfa Estimuladora de Ligação a CCAAT
/
Quinazolinonas
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article