Novel multitarget inhibitors with antiangiogenic and immunomodulator properties
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Otros documentos de la autoría: Conesa Milián, Laura; Falomir, Eva; Murga, Juan; Carda, Miguel; Marco, J. Alberto
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INVESTIGACIONMetadatos
Título
Novel multitarget inhibitors with antiangiogenic and immunomodulator propertiesFecha de publicación
2019-03-08Editor
ElsevierCita bibliográfica
CONESA MILIÁN, Laura; FALOMIR, Eva; MURGA, Juan; CARDA, Miguel; MARCO, J. Alberto (2019). Novel multitarget inhibitors with antiangiogenic and immunomodulator properties. European Journal of Medicinal Chemistry, v. 170, p. 87-98Tipo de documento
info:eu-repo/semantics/articleVersión de la editorial
https://www.sciencedirect.com/science/article/pii/S0223523419302235Versión
info:eu-repo/semantics/submittedVersionPalabras clave / Materias
Resumen
By means of docking studies, seventeen compounds T.1-T17 have been designed and evaluated as multitarget inhibitors of VEGFR-2 and PD-L1 proteins in order to overcome resistance phenomena offered by cancer. All these ... [+]
By means of docking studies, seventeen compounds T.1-T17 have been designed and evaluated as multitarget inhibitors of VEGFR-2 and PD-L1 proteins in order to overcome resistance phenomena offered by cancer. All these designed molecules display a urea moiety as a common structural feature and eight of them (T.1-T8) further contain a 1,2,3-triazol moiety. The antiproliferative activity of these molecules on several tumor cell lines (HT-29, MCF-7, HeLa, A549, HL-60), on the endothelial cell line HMEC-1 and on the non-tumor cell line HEK-293 has been determined. The urea derivatives were also evaluated for their antiangiogenic properties, whereby their ability to inhibit tubulogenesis and kinase activity employing flow cytometry, ELISA, immunofluorescence and western blot techniques was measured. In addition, these techniques were also employed to investigate the immunomodulator action of the synthetic compounds on the inhibition of PD-L1 and c-Myc proteins. Compound T.2, 1-(3-chlorophenyl)-3-(2-(4-(4-methoxybenzyl)-1H-1,2,3-triazol-1-yl)ethyl)urea, has shown similar results to sorafenib in both down-regulation of VEGFR-2 and inhibition of the kinase activity of this receptor. Furthermore, compound T.14, (E)-1-(4-chlorophenyl)-3-(3-(4-methoxystyryl)phenyl)urea, improves the effect of T.2 as regards tube formation of endothelial cells and inhibition of VEGFR-2 tyrosine kinase activity. In addition, T.14 improves the effect of the experimental drug BMS-8 in the inhibition of PD-L1 and c-Myc proteins. [-]
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European Journal of Medicinal Chemistry (2019), v. 170Proyecto de investigación
1) Ministerio de Economía y Competitividad (project CTQ2014-52949-P); 2) Universitat Jaume I (projects PI-1B2015-75 and UJI-B2018-38); 3) Spanish Ministry of Education, Culture and Sport for an FPU fellowship (FPU14/00878).Derechos de acceso
http://rightsstatements.org/vocab/CNE/1.0/
info:eu-repo/semantics/openAccess
info:eu-repo/semantics/openAccess
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