Utilize este identificador para referenciar este registo: http://hdl.handle.net/10198/8554
Título: 1-Aryl-3-[4-(thieno[3,2-d]pyrimidin-4-yloxy)phenyl]ureas as VEGFR-2 tyrosine kinase inhibitors: Synthesis, biological evaluation, and molecular modelling studies
Autor: Soares, Pedro
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.
Palavras-chave: Thienopyrimidine ether ureas
VEGFR-2 inhibitors
HUVECs
Western-blot
Molecular modelling
Data: 2013
Editora: Hindawi Publishing Corporation
Citação: Soares, Pedro; 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. (2013). 1-Aryl-3-[4-(thieno[3,2-d]pyrimidin-4-yloxy)phenyl]ureas as VEGFR-2 tyrosine kinase inhibitors: Synthesis, biological evaluation, and molecular modelling studies. BioMed Research International. ISSN 2314-6141. 2013, p. 1-9
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.
Peer review: yes
URI: http://hdl.handle.net/10198/8554
ISSN: 2314-6141
Aparece nas colecções:CIMO - Artigos em Revistas Indexados à WoS/Scopus

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