Copper( II) complexes based on tripodal pyridyl amine derivatives as efficient anticancer agents

The complexes [Cu(TPA)Cl]ClO(4)1/2H(2)O (1-ClO4), [Cu(6-MeTPA)Cl]ClO4/PF6 (2-ClO4/2-PF6), [Cu(6-Me(2)TPA)Cl]PF6 (3-PF6), [Cu(BPQA)Cl]ClO4/PF6 (4-ClO4/4-PF6), [Cu(BPQA)Cl]ClO4/PF6 (4-ClO4/4-PF6), [Cu(BQPA)Cl]ClO4/PF6 (5-ClO4/PF6), [Cu(L-1)Cl]ClO4/PF6 (6-ClO4/6-PF6), [Cu(L-2)Cl]ClO4 (7-ClO4) and [Cu(L-3)Cl]ClO4 (8-ClO4) have been synthesized and structurally characterized by spectroscopic techniques and single X-ray crystallography. The in vitro cytotoxicity of the prepared Cu(ii) complexes was evaluated against A2780 (ovarian), A2780R (cisplatin-resistant variant) and MCF7 (breast cancer) human cancer cell lines. Overall, the complexes revealed significant-to-moderate cytotoxicity, with the best results obtained for the complexes [Cu(BQPA)Cl]ClO4 (5-ClO4) and [Cu(BQPA)Cl]PF6 (5-PF6), showing IC50 values within the range of 4.7-10.8 M. The ability of the most cytotoxic complexes to cleave DNA under different conditions and the mechanisms underlying this activity were assessed by means of agarose gel electrophoresis.