Novel multitarget inhibitors with antiangiogenic and immunomodulator properties
View/ Open
Impact
Scholar |
Other documents of the author: Conesa Milián, Laura; Falomir, Eva; Murga, Juan; Carda, Miguel; Marco, J. Alberto
Metadata
Show full item recordcomunitat-uji-handle:10234/9
comunitat-uji-handle2:10234/7053
comunitat-uji-handle3:10234/8639
comunitat-uji-handle4:
INVESTIGACIONMetadata
Title
Novel multitarget inhibitors with antiangiogenic and immunomodulator propertiesDate
2019-03-08Publisher
ElsevierBibliographic citation
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. 87-98Type
info:eu-repo/semantics/articlePublisher version
https://www.sciencedirect.com/science/article/pii/S0223523419302235Version
info:eu-repo/semantics/submittedVersionSubject
Abstract
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. [-]
Is part of
European Journal of Medicinal Chemistry (2019), v. 170Investigation project
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).Rights
http://rightsstatements.org/vocab/CNE/1.0/
info:eu-repo/semantics/openAccess
info:eu-repo/semantics/openAccess
This item appears in the folowing collection(s)
- QUIO_Articles [689]