Synthesis of new N-, O-, S- and P-donor systems and related metal complexes with applications in bioinorganic and radiopharmaceutical chemistry

The wide success of cisplatin, in the clinical treatment of various types of neoplasias, has placed coordination chemistry of metal-based drugs in the front line in the fight against cancer. Although highly effective in treating a variety of cancers, the cure with cisplatin is still limited by several side effects and by inherited or acquired resistance phenomena. In the extensive research for other cytotoxic metal-based agents with improved pharmacological properties, complexes of group 11 metals showed encouraging perspectives. The aim of research group is the synthesis of new N-, O-, S- and P-donor systems and the development of innovative metal complexes valuable on the basis of the structural features, the redox properties and the ability of the ligand to selectively complex the metal. Particular attention has been addressed to the synthesis of water soluble copper(I) complexes showing in vitro antitumor activity, for example [HC(CO2)(pzMe2)2Cu(thp)2] and [HC(CO2)(tz)2Cu(thp)2], nitroimidazole and glucosamine conjugated heteroscorpionate ligands and related copper(II) complexes and group 11 metal compounds, such as [M(L)4][PF6] (M = Cu(I), Ag(I) or Au(I), L = tris(hydroxymethyl)phosphine, 1,3,5-triaza-7-phosphaadamantane or tris(hydroxypropyl)phosphine), with applications as radiopharmaceuticals and as anticancer agents. This research group has also focused on synthesizing novel N2S2- and N3S2-donor macrocyclic ligands based on the L,L-ethylenedicysteine skeleton, the related cold copper(II) and radioactive 64Cu(II) complexes useful as radiopharmaceuticals.