Utilize este identificador para referenciar este registo:
https://hdl.handle.net/1822/63796
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Campo DC | Valor | Idioma |
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dc.contributor.author | Soares, Pedro | por |
dc.contributor.author | Costa, Raquel | por |
dc.contributor.author | Froufe, Hugo J. C. | por |
dc.contributor.author | Calhelha, Ricardo C. | por |
dc.contributor.author | Peixoto, Daniela | por |
dc.contributor.author | Ferreira, Isabel C. F. R. | por |
dc.contributor.author | Abreu, Rui M. V. | por |
dc.contributor.author | Soares, Raquel | por |
dc.contributor.author | Queiroz, Maria João R. P. | por |
dc.date.accessioned | 2020-02-07T10:38:55Z | - |
dc.date.available | 2020-02-07T10:38:55Z | - |
dc.date.issued | 2013 | - |
dc.identifier.issn | 2314-6133 | por |
dc.identifier.uri | https://hdl.handle.net/1822/63796 | - |
dc.description.abstract | The vascular endothelial growth factor receptor-2 (VEGFR-2) is a tyrosine kinase receptor involved in the growth and differentiation of endothelial cells that are 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, showing also a significant proliferation inhibition of VEGF-stimulated human umbilical vein endothelial cells (HUVECs) at low concentrations (0.5-1 µM), using the Bromodeoxyuridine (BrdU) assay, not affecting cell viability. 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 performed and discussed using molecular docking studies. | por |
dc.description.sponsorship | The authors would like to acknowledge Foundation for the Science and Technology (FCT Portugal) for financial support through the NMR Portuguese network (Bruker 400 Avance III-Univ Minho). FCT and European Fund for Regional Development (FEDER)-COMPETE-QREN-EU for financial support through the research unities PEstC/QUI/UI686/2011, PEst-OE/SAU/UI0038/2011, and PEstOE/AGR/UI0690/2011, the research project PTDC/QUIQUI/111060/2009, and the post-Doctoral Grant attributed to Ricardo C. Calhelha (SFRH/BPD/68344/2010) also financed by Human Potential Operational Programme (POPH) and Social European Fund (FSE). | por |
dc.language.iso | eng | por |
dc.publisher | Hindawi Limited | por |
dc.relation | PEstC/QUI/UI686/2011 | por |
dc.relation | info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/PEst-OE%2FSAU%2FUI0038%2F2011/PT | por |
dc.relation | info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/PEst-OE%2FAGR%2FUI0690%2F2011/PT | por |
dc.relation | info:eu-repo/grantAgreement/FCT/5876-PPCDTI/PTDC%2FQUI-QUI%2F111060%2F2009/PT | por |
dc.relation | info:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBPD%2F68344%2F2010/PT | por |
dc.rights | openAccess | por |
dc.subject | Binding Sites | por |
dc.subject | Human Umbilical Vein Endothelial Cells | por |
dc.subject | Humans | por |
dc.subject | Models, Molecular | por |
dc.subject | Molecular Docking Simulation | por |
dc.subject | Neoplasms | por |
dc.subject | Neovascularization, Pathologic | por |
dc.subject | Phenylurea Compounds | por |
dc.subject | Protein Binding | por |
dc.subject | Protein Kinase Inhibitors | por |
dc.subject | Pyrimidines | por |
dc.subject | Vascular Endothelial Growth Factor Receptor-2 | por |
dc.title | 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 | por |
dc.type | article | por |
dc.peerreviewed | yes | por |
dc.relation.publisherversion | https://www.hindawi.com/journals/bmri/2013/154856/ | por |
oaire.citationVolume | 2013 | por |
dc.identifier.doi | 10.1155/2013/154856 | por |
dc.identifier.pmid | 23936775 | por |
dc.subject.wos | Science & Technology | por |
sdum.journal | Biomed Research International | por |
Aparece nas coleções: | DBio - Artigos/Papers |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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154856.pdf | 2,33 MB | Adobe PDF | Ver/Abrir |