Exploring the DNA binding, oxidative cleavage, and cytotoxic properties of new ternary copper(II) compounds containing 4-aminoantipyrine and N,N-heterocyclic co-ligands
2019
Abstract Herein we report on the synthesis and characterization of new water-soluble complexes with the basic formula [Cu(O N)(N N)(ClO 4 ) 2 ], where O N = 4-aminoantipyrine and N N = 1,10-phenanthroline ( 1 ) or 2,2ʹ-bipyridine ( 2 ). Both complexes have distorted tetragonal geometry around each copper centre, which is coordinated to both bidentate ligands in equatorial sites with two perchlorate ions weakly bonded in the axial positions. The compounds bind to DNA and induce oxidative DNA damage mediated by reactive oxygen species (ROS). Both complexes inhibit the growth of K562 cells in a concentration-dependent manner with IC 50 values lower than the corresponding free ligands. Significantly, the most cytotoxic agent (complex 1 ) presented high in vitro nucleolytic activity by generating single- and double-strand breaks, besides of inhibiting topoisomerase I enzymatic activity at low micromolar concentration.
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