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

Abstract

The complexes [Cu(TPA)Cl]ClO₄·½H₂O (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.