Detalhes bibliográficos
| Autor(a) principal: |
Soares, Pedro |
| Data de Publicação: |
2013 |
| Outros Autores: |
Costa, Raquel,
Froufe, Hugo J.C.,
Calhelha, Ricardo C.,
Peixoto, Daniela,
Abreu, Rui M.V.,
Ferreira, Isabel C.F.R.,
Soares, Raquel,
Queiroz, Maria João R.P. |
| Tipo de documento: |
Artigo
|
| Idioma: |
eng |
| Título da fonte: |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: |
http://hdl.handle.net/10198/8554
|
Resumo: |
The Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2) is a tyrosine kinase receptor involved in the growth and differentiation of endothelial cells that is implicated in tumor-associated angiogenesis. In this study novel 1-aryl-3-[4-(thieno[3,2-d]pyrimidin-4-yloxy)phenyl]ureas were synthesized and evaluated for the VEGFR-2 tyrosine kinase inhibition. Three of these compounds showed good VEGFR-2 inhibition presenting low IC50 values (150-199 nM) in enzymatic assays. The latter promoted also significant inhibition of cell proliferation at low concentrations (0.5-1 µM), not affecting cell viability, of VEGF-stimulated Human Umbilical Vein Endothelial Cells (HUVECs) using the BrdU assay. The determination of the total and phosphorylated (active) VEGFR-2 was performed by western-blot, and it was possible to conclude that the compounds significantly inhibit the phosphorylation of the receptor at 1 µM pointing to their antiproliferative mechanism of action in HUVECs. The molecular rationale for inhibiting the tyrosine kinase domain of VEGFR-2 was also done and discussed using molecular docking studies. |