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

Article abstract of DOI:10.1039/c9nj00061e

The complexes [Cu(TPA)Cl]ClO₄·?H₂O (1-ClO₄), [Cu(6-MeTPA)Cl]ClO₄/PF₆ (2-ClO₄/2-PF₆), [Cu(6-Me₂TPA)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(L¹)Cl]ClO₄/PF₆ (6-ClO₄/6-PF₆), [Cu(L²)Cl]ClO₄ (7-ClO₄) and [Cu(L³)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 μM. 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.