Ligand-Dependent DNA Binding and Cytotoxicity of Palladium(II) Complexes

In the search for alternatives to platinum anticancer drugs, palladium complexes have attracted considerable interest. In this frame, six square planar palladium(II) complexes with the general formula [PdAB₂] were prepared, where the ligand A is (1R,2R)-diaminocyclohexane (DACH) or 1,10-phenanthroline (Phen), and the ligand B is chlorine, iodine, or pyridine. The biological properties of the investigated compounds were systematically evaluated to identify trends linked to ligand variations. The complexes were synthesized following established experimental procedures and characterized by elemental analysis and NMR spectroscopy. DNA interactions were investigated through melting experiments and the ethidium bromide (EB) displacement assay. The obtained data suggested covalent adduct formation as the preferential binding mode for the DACH-containing complexes, whereas intercalation was predominant for the phenanthroline-based complexes. Notably, at least one compound appears to interact with DNA through both modes. Cytotoxic activity was evaluated against three human ovarian cancer cell lines (A2780, A2780R, and SKOV3) as well as a healthy control cell line (HSkM, human skeletal myoblasts). Significant cytotoxic activity was observed for the Phen-containing complexes, with compound 3 also showing a good selectivity index. Conversely, DACH-containing complexes were found to be non-cytotoxic.