Synthesis and evaluation of N-(benzofuran-5-yl)aromaticsulfonamide derivatives as novel HIF-1 inhibitors that possess anti-angiogenic potential.
Bioorg Med Chem
; 25(6): 1737-1746, 2017 03 15.
Article
em En
| MEDLINE
| ID: mdl-28209257
ABSTRACT
Hypoxia-inducible factor-1 (HIF-1) as a key mediator in tumor metastasis, angiogenesis, and poor patient prognosis has been recognized as an important cancer drug target. A novel series of N-(benzofuran-5-yl)aromaticsulfonamide derivatives were synthesized and evaluated as HIF-1 inhibitor. Among these compounds, 7q exhibited specific inhibitory effects on HIF-1 by downregulating the expression of HIF-1α under hypoxic conditions. It inhibited the HIF-1 transcriptional activity (IC50=12.5±0.7µM) and secretion of VEGF (IC50=18.8µM) in MCF-7 cells. Meanwhile, it also significantly suppressed hypoxia-induced migration of HUVEC cells in nontoxic concentrations. Additionally, tube formation assay demonstrated its anti-angiogenesis activity. Finally, the in vivo study indicated that compound 7q could retard angiogenesis in CAM model. These findings supported the HIF-1 inhibitory effect and anti-angiogenic potential of this class of compounds as HIF-1 inhibitor.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Sulfonamidas
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Benzofuranos
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Inibidores da Angiogênese
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Fator 1 Induzível por Hipóxia
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article