Design, synthesis, and evaluation of novel ursolic acid derivatives as HIF-1α inhibitors with anticancer potential.
Bioorg Chem
; 75: 157-169, 2017 12.
Article
em En
| MEDLINE
| ID: mdl-28950243
ABSTRACT
Hypoxia-inducible factor-1α (HIF-1α), a key mediator in tumor metastasis and angiogenesis, is associated with poor patient prognosis and has been recognized as an important cancer drug target. In this work, four novel series of ursolic acid derivatives containing oxadiazole, triazolone, and piperazine moieties were designed, synthesized, and evaluated for anti-tumor activity as HIF-1α inhibitors. The majority of the compounds showed an excellent ability to inhibit the expression of HIF-1α. In particular, 11b inhibited HIF-1α transcriptional activity under hypoxic conditions with IC50=36.9µM. The cytotoxicity of these compounds was also assessed in human colon cancer cell HCT116 cells by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, and no compounds showed any appreciable cytotoxic activity (IC50>100µmol/L), which was lower than that of ursolic acid (IC50=23.8µmol/L). The mechanism of action of the representative compound 11b was also investigated.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Triterpenos
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Desenho de Fármacos
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Subunidade alfa do Fator 1 Induzível por Hipóxia
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Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article