RESUMO
Homoleptic, tetrahedral Cu(i) complexes of the type [Cu(P)4]BF4 (1-3), where P are the phosphine ligands, 1,3,5-triaza-7-phosphaadamantane (PTA), 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane (DAPTA) and 2-thia-1,3,5-triaza-phosphoaadamantane-2,2-dioxide (PTA-SO2), have been prepared. Novel complexes [Cu(DAPTA)4]BF42 and [Cu(PTA-SO2)4]BF43 have been fully characterized by means of spectroscopic methods, corroborated by XAS-EXAFS analysis of 2. In vitro cell culture experiments revealed a significant antiproliferative activity for Cu(i) compounds against several human cancer cell lines derived from solid tumors with preferential cell growth inhibition towards tumour compared to non-malignant cells. In vitro monitoring of migration and capillary-like tube formation of human umbilical vein endothelial cells (HUVECs) showed an anti-angiogenic effect of copper(i) complexes at sub-cytotoxic concentrations. In vivo studies on the antitumor efficacy and ability to inhibit angiogenesis confirmed the dual cytotoxic and anti-angiogenic properties of Cu(i) derivatives.
Assuntos
Inibidores da Angiogênese/farmacologia , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Cobre/farmacologia , Fosfinas/farmacologia , Adamantano/análogos & derivados , Inibidores da Angiogênese/química , Inibidores da Angiogênese/toxicidade , Animais , Antineoplásicos/química , Antineoplásicos/toxicidade , Peso Corporal/efeitos dos fármacos , Linhagem Celular Tumoral , Complexos de Coordenação/química , Complexos de Coordenação/toxicidade , Cobre/química , Cobre/toxicidade , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neovascularização Patológica/induzido quimicamente , Compostos Organofosforados , Fosfinas/química , Fosfinas/toxicidadeRESUMO
Bovine plasma amine oxidase was covalently bound to CH-Sepharose 4B by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride. The immobilized enzyme showed no significant change in specific activity when spermidine was the substrate, while the enzyme affinity toward benzylamine and propylamine increased significantly. Similarly, the pig kidney diamine oxidase physically adsorbed to Con A-Sepharose showed large changes in affinity toward substrates such as p-dimethylaminoethylbenzylamine with respect to the native enzyme. These changes are discussed in terms of active site modification as a consequence of the enzyme immobilization.