Correlation between DNA interactions and cytotoxic activity of four new ternary compounds of copper(II) with N-donor heterocyclic ligands

Four new ternary complexes of copper(II) were synthesized and characterized: [Cu(hyd)(bpy)(acn)(ClO4)](ClO4)] (1), [Cu(hyd)(phen)(acn)(ClO4)](ClO4)] (2), [Cu(Shyd)(bpy)(acn)(ClO4)](ClO4)1 (3) and [Cu(Shyd)(phen)(acn) (ClO4)](ClO4)] (4), in which acn = acetonitrile; hyd = 2-furoic acid hydrazide, bpy = 2,2-bipyridine; phen = 1,10-phenanthroline and Shyd = 2-thiophenecarboxylic acid hydrazide. The cytotoxic activity of the complexes in a chronic myelogenous leukemia cell line was investigated. All complexes are able to enter cells and inhibit cellular growth in a concentration-dependent manner, with an activity higher than that of the corresponding free ligands. The substitution of Shyd for hyd increases the activity, while the substitution of bpy for phen renders the complex less active. Therefore, the most potent complex is 4 with an IC50 value of 1.5 +/- 02 mu M. The intracellular copper concentration needed to inhibit 50% of cell growth is approximately 7 x 10(-15) mol/cell. It is worth notifying that a correlation between cytotoxic activity, DNA binding affinity and DNA cleavage was found: 1 < 3 < 2 < 4. (C) 2013 Elsevier Inc. All rights reserved.