Antiproliferative activity of nickel(II), palladium(II) and zinc(II) thiosemicarbazone complexes

Complexes of nickel(II), palladium(II) and zinc(II) have been synthesized with four ONS thiosemicarbazone tridentate ligands. The ligands were obtained from the synthesis of 2-hydroxy-3-methoxybenzaldehyde or 2,3-dihydroxybenzaldehyde with thiosemicarbazide or 4-ethyl-3-thiosemicarbazide. The palladium and zinc complexes have formula [ML](2) (H2L, ligand), whereas in the case of nickel, two different types of complexes are formed: [NiL](2) or [Ni(HL)(2)] depending on the starting metal ion:ligand ratio (1:1 or 1:2, respectively). The nickel (II) complex [Ni(H2L)(HL)](CH3COO) was characterized also by single crystal X-ray diffraction. While the ligands did not exhibit antiproliferative activity on human histiocytic lymphoma U937 cells, the metal complexes showed GI(50) values ranging from approximately 20 to 39 mu M. The most promising metal complexes were also tested through Alkaline Comet Assay: while with the ligand DNA damages were not detected even at the highest ligand concentrations (100 mu M), the complexes, and in particular the nickel dimers [NiL](2), exhibit genotoxic activity.