A novel series of monofunctional Pt(II) complexes framed on 8-aminoquinoline: synthesis and antiproliferative studies

8-aminoquinoline and its derivatives are heterocyclic compounds that are drawing attention in the field of bioorganometallic chemistry due to their metal-binding ability along with a variety of biological effects.1 From a structural point of view, the presence of two nitrogen donor atoms make them bidentate chelating ligands able to form thermodynamically stable coordinative complexes with metal ions thus providing them with novel biochemical properties. Taken together these features, 8-aminoquinolines are beheld as a privileged framework for the preparation of new metallodrug candidates.2,3 Our research group have recently reported a series of cationic triamine platinum complexes in which the addition of an alkylated imidazole ligand to the dichloro neutral precursor led to charged platinum complexes eliciting a novel cytotoxic profile involving mechanisms of action not related to a simple DNA crosslinking as established for cisplatin. Here, we reported the synthesis and cytotoxicity evaluation of a series of platinum complexes using 8-aminoquinoline and its chiral 5,6,7,8-tetrahydro-derivatives as chelating ligands and in which a differently and opportunely alkylated imidazole was used to prepare the corresponding monofunctional platinum complexes. The preliminary cytotoxicity evaluation on the lead compound was carried out on the highly aggressive MDA-MB-231 invasive and poorly differentiated triple-negative breast cancer (TNBC) cell line furnishing a significant IC50 4.5±0.5µM