Apoptotic induction in K562 cell line by new water-soluble complexes of nickel(II) and zinc(II)

Abstract

New water-soluble Zn(II) and Ni(II) complexes with three thiosemicarbazone ligands, modified by substitution (H, Me, Ph), H2L1Cl, H2L2Cl and H2L3Cl were synthesized through the reaction of the ligands with chloride salts of metals. All complexes were characterized by physico-chemical techniques. Elemental analysis and X-ray crystallography confirmed that metal to ligand ratio 1:2 in nickel(II) complexes and 1:1 in zinc(II) complexes. In the mononuclear Ni-H2L1Cl complex, the nickel(II) centre is surrounded by two ligands in distorted octahedral geometry. Both ligands are tridentate, nitrogen, sulfur, and oxygen donors (NSO), in thione form, with oxygen atom acting as phenolate in one of the ligands while in the other it coordinates as phenol. In the Zn-H2L1Cl complex, the ligand acts as monodentate through sulfur atom in thione form. Geometry around the zinc(II) is tetrahedral, with remaining positions occupied by three chloride anions, resulting in Cl3S environment around the metal. All of the complexes showed good solubility and stability in aqueous media. The cytotoxic effect of the complexes was measured using the MTT assay on MCF-7 and K562 cell lines, and the results showed that Zn-H2L2Cl had lower IC50 values compared to the other compounds. Flow cytometry analysis on the K562 cells showed the apoptosis cell death after treating with the Zn-H2L2Cl. Cell cycle studies confirmed the cell cycle arrest in sub-G1 phase for Zn-H2L2Cl.