Synthesis and biological evaluation as antiangiogenic agents of ureas derived from 3′-aminocombretastatin A-4
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Other documents of the author: Conesa Milián, Laura; Falomir, Eva; Murga, Juan; Carda, Miguel; Marco, J. Alberto
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Show full item recordcomunitat-uji-handle:10234/9
comunitat-uji-handle2:10234/7053
comunitat-uji-handle3:10234/8639
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https://doi.org/10.1016/j.ejmech.2018.11.023 |
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Title
Synthesis and biological evaluation as antiangiogenic agents of ureas derived from 3′-aminocombretastatin A-4Date
2019-01-15Publisher
ElsevierBibliographic citation
CONESA MILIÁN, Laura; FALOMIR, Eva; MURGA CLAUSELL, Juan; CARDA USÓ, Miguel; MARCO VENTURA, Juan Alberto (2019). Synthesis and biological evaluation as antiangiogenic agents of ureas derived from 3′-aminocombretastatin A-4. European Journal of Medicinal Chemistry, v. 162, p. 781-792Type
info:eu-repo/semantics/articleVersion
info:eu-repo/semantics/publishedVersionSubject
Abstract
Twenty-six compounds derived from 3′-aminocombretastatin A-4 (AmCA-4) containing a urea fragment mimicking the structure of Sorafenib, have been synthesized and evaluated as antiangiogenic compounds. Antiproliferative ... [+]
Twenty-six compounds derived from 3′-aminocombretastatin A-4 (AmCA-4) containing a urea fragment mimicking the structure of Sorafenib, have been synthesized and evaluated as antiangiogenic compounds. Antiproliferative activity of all the synthetic ureas has been measured on tumor cell lines HT-29, MCF-7, HeLa, A-549 and HL-60 as well as on the endothelial cell line HMEC-1 and on the non-tumor cell line HEK-293. Preliminary docking studies were developed in order to predict which ureas show better interactions with the protein VEGFR-2. Then, the selected derivatives were evaluated in terms of their apoptotic effect and antiangiogenic properties. In this regard, VEGFR-2/ligand interactions were determined by flow cytometry and immunofluorescence techniques. Inhibition of VEGFR-2 tyrosine kinase activity in both the A-549 and HMEC-1 cell lines was also carried out. In addition, tube formation inhibition was studied in endothelial cells. Ortho-chloro substituted urea 5 and ortho-bromo substituted urea 8 were the most active ones in both down-regulation of VEGFR-2 and inhibition of the kinase activity of this receptor, with better results than those obtained with sunitinib and sorafenib. [-]
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European Journal of Medicinal Chemistry (2019), v. 162Investigation project
1) Ministerio de Economía y Competitividad (project CTQ2014-52949-P); 2) Universitat Jaume I (project PI-1B2015-75); 3) Conselleria d’Educació, Investigació, Cultura i Sport de la Generalitat Valenciana (project PROMETEO 2013/027); 4) Spanish Ministry of Education, Culture and Sport for the FPU fellowship (FPU14/00878).Rights
http://rightsstatements.org/vocab/CNE/1.0/
info:eu-repo/semantics/restrictedAccess
info:eu-repo/semantics/restrictedAccess
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