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Int J Mol Sci ; 23(13)2022 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-35806053

RESUMEN

Twenty-six triazole-based derivatives were designed for targeting both PD-L1 (programmed death receptor ligand 1) and VEGFR-2 (vascular endothelial growth factor receptor 2). These compounds were synthetized and biologically evaluated as multitarget inhibitors of VEGFR-2, PD-L1 and c-Myc proteins. The antiproliferative activity of these molecules on several tumor cell lines (HT-29, A-549, and MCF-7) and on the non-tumor cell line HEK-293 was determined. The effects on the abovementioned biological targets were evaluated for some selected compounds. Compound 23, bearing a p-chlorophenyl group, showed better results than sorafenib in regard to the downregulation of VEGFR-2 and a similar effect to BMS-8 on both PD-L1 and c-Myc proteins. The antiangiogenic and antivascular activities of chloro derivatives were also established by endothelial microtube formation assay on Matrigel®.


Asunto(s)
Antineoplásicos , Receptor 2 de Factores de Crecimiento Endotelial Vascular , Antígeno B7-H1 , Línea Celular Tumoral , Proliferación Celular , Ensayos de Selección de Medicamentos Antitumorales , Células HEK293 , Humanos , Simulación del Acoplamiento Molecular , Proteínas Proto-Oncogénicas c-myc/metabolismo , Relación Estructura-Actividad , Triazoles/farmacología , Factor A de Crecimiento Endotelial Vascular/farmacología , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo
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