Novel quinazolin-4-one derivatives as potentiating agents of doxorubicin cytotoxicity.
Bioorg Chem
; 82: 204-210, 2019 02.
Article
em En
| MEDLINE
| ID: mdl-30326402
ABSTRACT
We report the design, synthesis and biological evaluation of 17 novel 8-aryl-2-morpholino-3,4-dihydroquinazoline derivatives based on the standard model of DNA-PK and PI3K inhibitors. Novel compounds are sub-divided into two series where the second series of five derivatives was designed to have a better solubility profile over the first one. A combination of in vitro and in silico techniques suggested a plausible synergistic effect with doxorubicin of the most potent compound 14d on cell proliferation via DNA-PK and poly(ADP-ribose) polymerase-1 (PARP-1) inhibition, while alone having a negligible effect on cell proliferation.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doxorrubicina
/
Morfolinas
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Inibidores Enzimáticos
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Quinazolinonas
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Antineoplásicos
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Bioorg Chem
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
República Tcheca