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
Joint Authors
Soares, Pedro
Costa, Raquel
Froufe, Hugo J. C.
Calhelha, Ricardo C.
Peixoto, Daniela
Abreu, Rui M. V.
Soares, Raquel
Ferreira, Isabel C. F. R.
Queiroz, Maria-João R. P.
Source
Issue
Vol. 2013, Issue 2013 (31 Dec. 2013), pp.1-9, 9 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2013-07-07
Country of Publication
Egypt
No. of Pages
9
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Soares, Pedro& Costa, Raquel& Froufe, Hugo J. C.& Calhelha, Ricardo C.& Peixoto, Daniela& Ferreira, Isabel C. F. R.…[et al.]. 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،Vol. 2013, no. 2013, pp.1-9.
https://search.emarefa.net/detail/BIM-1030139
Modern Language Association (MLA)
Soares, Pedro…[et al.]. 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 No. 2013 (2013), pp.1-9.
https://search.emarefa.net/detail/BIM-1030139
American Medical Association (AMA)
Soares, Pedro& Costa, Raquel& Froufe, Hugo J. C.& Calhelha, Ricardo C.& Peixoto, Daniela& Ferreira, Isabel C. F. R.…[et al.]. 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. 2013. Vol. 2013, no. 2013, pp.1-9.
https://search.emarefa.net/detail/BIM-1030139
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1030139