RESUMO
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.
Assuntos
Inibidores da Angiogênese/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Cobre/química , Inibidores da Angiogênese/química , Inibidores da Angiogênese/metabolismo , Antineoplásicos/metabolismo , Linhagem Celular , Complexos de Coordenação/metabolismo , Cristalografia por Raios X , Quadruplex G , Células HeLa , Células Endoteliais da Veia Umbilical Humana , Humanos , Concentração de Íons de Hidrogênio , Ligantes , Conformação Molecular , Fenantrolinas/química , Regiões Promotoras Genéticas , Ligação Proteica , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Albumina Sérica/química , Albumina Sérica/metabolismo , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
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.
