Design, synthesis and biological evaluation of 4-(pyridin-4-yloxy)benzamide derivatives bearing a 5-methylpyridazin-3(2H)-one fragment.
Bioorg Med Chem Lett
; 30(9): 127076, 2020 05 01.
Article
em En
| MEDLINE
| ID: mdl-32173195
ABSTRACT
A series of 4-(pyridin-4-yloxy)benzamide derivatives bearing a 5-methylpyridazin-3(2H)-one fragment were designed, synthesized, and evaluated for their biological activity. Most compounds showed effective inhibitory activity against cancer cell lines of A549, HeLa and MCF-7. Among them, the most promising compound 40 showed excellent activity against A549, HeLa and MCF-7 cell lines with IC50 values of 1.03, 1.15 and 2.59 µM, respectively, which was 2.606.95 times more active than that of Golvatinib. The structure-activity relationships (SARs) showed that the introduction of 5-methylpyridazin-3(2H)-one to "5-atom linker" and the modification of the amide with morpholine group were beneficial for enhancing the inhibitory activity of compounds. In addition, the further research on compound 40 mainly include c-Met kinase activity, concentration dependence, apoptosis (acridine orange staining), and molecular docking.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Benzamidas
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Desenho de Fármacos
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Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2020
Tipo de documento:
Article