Synthesis and anti-hepatocellular carcinoma activity of aminopyridinol-sorafenib hybrids.
J Enzyme Inhib Med Chem
; 36(1): 1884-1897, 2021 Dec.
Article
em En
| MEDLINE
| ID: mdl-34340602
ABSTRACT
Sorafenib is recommended as the primary therapeutic drug for patients with hepatocellular carcinoma. To discover a new compound that avoids low response rates and toxic side effects that occur in sorafenib therapy, we designed and synthesized new hybrid compounds of sorafenib and 2,4,5-trimethylpyridin-3-ols. Compound 6 was selected as the best of 24 hybrids that inhibit each of the four Raf kinases. The anti-proliferative activity of 6 in HepG2, Hep3B, and Huh7 cell lines was slightly lower than that of sorafenib. However, in H6c7 and CCD841 normal epithelial cell lines, the cytotoxicity of 6 was much lower than that of sorafenib. In addition, similar to sorafenib, compound 6 inhibited spheroid forming ability of Hep3B cells in vitro and tumour growth in a xenograft tumour model of the chick chorioallantoic membrane implanted with Huh7 cells. Compound 6 may be a promising candidate targeting hepatocellular carcinoma with low toxic side effects on normal cells.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirimidinas
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Carcinoma Hepatocelular
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Sorafenibe
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Neoplasias Hepáticas
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Antineoplásicos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Enzyme Inhib Med Chem
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2021
Tipo de documento:
Article