In vivo antiproliferative activity of the phoshino copper(I) drug [Cu(thp)4][PF6]

Several studies report that tumour tissues have proved to be avid of copper. Tberefore, tumour cells may represent an appropriate, selective target for a properly designed copper-based antitumor drug. Non-tumour cells may promote, instead, elimination of excess copper through homeostatic mechanisms, as it happens under natural phases of the life characterized by the occurrence of neovascularization processes as embryonic and postembryonic deveìoprnent, reproductive cycle, wound repair, etc .. The interest of the inorganic chemistry community in the development of copper-based antitumor drugs has rapidly expanded in the last few years. Despite the huge number of complexes showing promising antitumor activity in in vitro tests (sometimes at nanomolar level), the transfer into in vivo models remains poorly practiced. Based on the above arguments, we have been testing the amiproliferative properties of the cationic copper(I) complex, (Cu(thp)4](PF6] (CP; thp = tris-hydroxymethylphosphine). CP is a bydrophilic derivative, stable toward metal disproportionation in aqueous media. The chemical structure of CP is tetrahedral in the solid state (X-ray) and in the solution state at 10-2 / 10-3 M concentrations. On the contrary, at 10-5 concentration CP was found to promote the forrnation of co-ordinatively unsaturated [Cu(thp)3]+, [Cu(thp)2]+, [Cu(thp)]+, species. In vitro assays have established that CP is an effective anticancer agent against several human cancer cells in vitro, and against murine Lewis lung carcinoma (LCC) in vivo.