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dc.contributor.authorConesa Milián, Laura
dc.contributor.authorFalomir, Eva
dc.contributor.authorMurga, Juan
dc.contributor.authorCarda, Miguel
dc.contributor.authorMarco, J. Alberto
dc.identifier.citationCONESA 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. 781-792ca_CA
dc.description.abstractTwenty-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.ca_CA
dc.format.extent12 p.ca_CA
dc.relation.isPartOfEuropean Journal of Medicinal Chemistry (2019), v. 162ca_CA
dc.subjectAminocombretastatin A-4ca_CA
dc.titleSynthesis and biological evaluation as antiangiogenic agents of ureas derived from 3′-aminocombretastatin A-4ca_CA
dc.relation.projectID1) 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).ca_CA

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