The search for novel metal-based antitumor drugs other than Pt agents includes the investigation of the cytotoxic activity of copper(I/II) compounds [1,2]. Among these copper agents, particular attention has recently been devoted to hydrophilic copper(I) species bearing phosphines because of their noteworthy stability in aqueous media accomplished with remarkable in vitro cytotoxic activities [3]. In this study we report on the synthesis, characterization of a series of Cu(I) complexes with tris(2-cyanoethyl)phosphine (PCN) and tris(2-carboxyethyl)phosphine (TCEP). They were prepared by reaction of the labile [Cu(MeCN)4]+ precursor with the pertinent phosphine giving compounds of the following formulation: [Cu(X)(PCN)] (X = Cl, Br), [Cu(MeCN)(PCN)]+, [Cu(PCN)2]+ and [Cu(TCEP)2]-. The new copper(I) complexes were tested for their cytotoxic properties against a panel of several human tumor cell lines also including cisplatin and multidrug resistant phenotypes. Moreover, in isolated mitochondria, copper(I) complexes were evaluated for their ability to alter the most relevant mitochondrial phato-physiological parameters such as respiration, coupling, ATP-synthetase activity and membrane potential.
In vitro cytotoxic activity of copper(I) complexes with tris(cyanoethyl)phoshine or tris(carboxyethyl)phosphine
PELLEI, Maura;SANTINI, Carlo;
2009-01-01
Abstract
The search for novel metal-based antitumor drugs other than Pt agents includes the investigation of the cytotoxic activity of copper(I/II) compounds [1,2]. Among these copper agents, particular attention has recently been devoted to hydrophilic copper(I) species bearing phosphines because of their noteworthy stability in aqueous media accomplished with remarkable in vitro cytotoxic activities [3]. In this study we report on the synthesis, characterization of a series of Cu(I) complexes with tris(2-cyanoethyl)phosphine (PCN) and tris(2-carboxyethyl)phosphine (TCEP). They were prepared by reaction of the labile [Cu(MeCN)4]+ precursor with the pertinent phosphine giving compounds of the following formulation: [Cu(X)(PCN)] (X = Cl, Br), [Cu(MeCN)(PCN)]+, [Cu(PCN)2]+ and [Cu(TCEP)2]-. The new copper(I) complexes were tested for their cytotoxic properties against a panel of several human tumor cell lines also including cisplatin and multidrug resistant phenotypes. Moreover, in isolated mitochondria, copper(I) complexes were evaluated for their ability to alter the most relevant mitochondrial phato-physiological parameters such as respiration, coupling, ATP-synthetase activity and membrane potential.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.