Antiproliferative activity of cationic and neutral thiosemicarbazone copper(II) complexes

The copper(II) complexes, [Cu(tscpy)(MeOH)](Cl) (1), [CuCl(mtscpy)] (2) and [CuCl(ptscpy)] (3) (where, Htscpy = pyridoxal thiosemicarbazone, Hmtscpy = pyridoxal N-4-methyl thiosemicarbazone and Hptscpy = pyridoxal N-4-phenylthiosemicarbazone) have been isolated and characterized by the aid of various analytical and spectral methods. The molecular structure of the cationic complex 1 and the neutral complex 3 were characterized by single crystal X-ray diffraction studies which revealed that the thiosemicarbazone ligands coordinated to the copper(II) centre as monoanionic tridentate (ONS-) forming five and six membered rings. The interaction of the new complexes with DNA has been explored using spectral and viscosity studies, indicating the complexes bind to DNA via partial intercalation. A predominantly hydrolytic cleavage of supercoiled pUC1(plasmid DNA was confirmed through an experiment performed in the presence of T4 ligase. Furthermore, the interactions of the complexes with serum albumin (BSA) were also investigated using fluorescence spectroscopic methods. The efficiency of the complexes in arresting the growth of human cervical cancer cells (HeLa), human breast cancer cell line (MCF-7) and human liver carcinoma cells (Hep G2) has also been studied along with the cell viability assay against the noncancerous NIH 3T3 mouse embryonic fibroblast cell lines under in vitro conditions. The cationic complex 1 has higher cytotoxic activity than the other two neutral complexes and cisplatin. AO-EB/DAPI staining assays, Annexin V-FITC and FACS analyses indicated that the complex 1 induces cell death only by apoptosis.