DNA and protein binding, double-strand DNA cleavage and cytotoxicity of mixed ligand copper(II) complexes of the antibacterial drug nalidixic acid

The complexes [Cu(nal)(diimine)(H2O)]+ [H(nal) = nalidixic acid, diimine = 2,2′-bipyridine, 1,10-phenanthroline, 5,6-dimethyl-1,10-phenanthroline] bind to DNA in minor groove while [Cu(nal)(3,4,7,8-tmp)(H2O)]+ [3,4,7,8-tmp = 3,4,7,8-tetramethyl-1,10-phenanthroline] binds in the major groove. The latter shows self-activated double-strand DNA cleavage and causes apoptotic cell death on MCF-7 cancer cells with potency higher than its analogues.91