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de Souza, Ívina P.; Machado, Bárbara de P.; de Carvalho, Alexandre B.; Binatti, Ildefonso; Krambrock, Klaus; Molphy, Zara; Kellett, Andrew; Pereira-Maia, Elene C.; Silva-Caldeira, Priscila P.
Journal of molecular structure, 02/2019, Volume: 1178Journal Article
Herein we report on the synthesis and characterization of new water-soluble complexes with the basic formula Cu(ON)(NN)(ClO4)2, where ON = 4-aminoantipyrine and NN = 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 IC50 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. We report two new Cu(II) complexes with 4-aminoantipyrine able to prevent topoisomerase I activity, induce DNA cleavage and inhibit the growth of cancer cells. Display omitted •Water-soluble Cu2+ complexes able to bind to DNA and induce oxidative DNA damage.•Inhibition of the growth of tumor cells (K562 cell line), IC50 = 1.8 μM.•Inhibition of topoisomerase I enzymatic activity at 5.0 μM.
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