RESUMEN
A novel copper(II) complex with mixed ligands including ß-[(3-formyl-5-methyl-2-hydroxy-benzylidene)amino]propionic acid anion and 1,10'-phenanthroline was synthesized, and its crystal structure was thoroughly characterized. It exerted excellent inducing apoptosis, anti-angiogenesis and antiproliferative properties in vitro. The complex can bind human serum albumin (HSA) at physiological pH conditions. Remarkably, it can induce formation of the mixed parallel/antiparallel G-quadruplex structures in the G-rich sequence of the proximal vascular endothelial growth factor (VEGF) promoter, and stabilize these G-quadruplex structures, which provide an opportunity for anti-angiogenesis chemotherapeutics. Furthermore, the complex showed a strong uptake, and exhibited multiple anticancer functions by inhibiting the expression of p-Akt and p-Erk1/2 proteins and by upregulating the levels of reactive oxygen species (ROS). Because of the reported results, this new copper(II) complex qualifies itself as a potential anticancer drug candidate.
Asunto(s)
Inhibidores de la Angiogénesis/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Cobre/química , Inhibidores de la Angiogénesis/química , Inhibidores de la Angiogénesis/metabolismo , Antineoplásicos/metabolismo , Línea Celular , Complejos de Coordinación/metabolismo , Cristalografía por Rayos X , G-Cuádruplex , Células HeLa , Células Endoteliales de la Vena Umbilical Humana , Humanos , Concentración de Iones de Hidrógeno , Ligandos , Conformación Molecular , Fenantrolinas/química , Regiones Promotoras Genéticas , Unión Proteica , Proteínas Proto-Oncogénicas c-akt/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Albúmina Sérica/química , Albúmina Sérica/metabolismo , Factor A de Crecimiento Endotelial Vascular/genéticaRESUMEN
The crystals of two binuclear copper-based complexes were obtained. One complex can remarkably induce apoptosis and inhibit angiogenesis to mediate tumour growth at a greater extent. Furthermore, this complex showed a strong energy-dependent and non-endocytotic uptake and exhibited multiple anti-cancer functions by inhibiting the expressions of p-Akt and p-Erk1/2 proteins and by decreasing the levels of reactive oxygen species.