Copper(ii) complexes based on tripodal pyridyl amine derivatives as efficient anticancer agents. (28th March 2019) - Massoud, Salah S.
Abstract : The in vitro cytotoxicity of a series of chlorido-Cu(ii ) complexes based on tripod pyridyl N4-donor derivatives revealed significant-to-moderate cytotoxicity against human cancer cell lines with the best results obtained for [Cu(BQPA)Cl]ClO4 /PF6 (5-ClO4 /PF6 ) with IC50 values of 4.7–10.8 μM. Abstract : The complexes [Cu(TPA)Cl]ClO4 ·½H2 O (1-ClO4 ), [Cu(6-MeTPA)Cl]ClO4 /PF6 (2-ClO4 /2-PF6 ), [Cu(6-Me2 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 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.