title: Analysis of the DNA interaction of copper compounds belonging to the Casiopeínas® antitumoral series.
abstract: Casiopeínas® are mixed-chelate copper complexes with antitumor tested potential. Their activity, both in vitro and in vivo, as antiproliferative, cytotoxic, and genotoxic drugs has been assessed. Biological results of these copper compounds have deserved some of them entering clinical trials. Significant efforts have been devoted to the in-depth identification of their mechanism of action. Using gel electrophoresis analysis, we have previously shown that the interaction of the Casiopeínas® Cas II-gly, [Cu(4,7-dimethyl-1,10-phenanthroline)(glycinate)]NO3 with DNA, triggers the cleavage of the biomolecule by a free radical mechanism. In this work, we further study the behavior of different complexes of the same Casiopeínas® series also including glycinate as co-ligand {Cas VI-gly (5,6 dimethyl-1,10-phenanthroline glycinato copper(II) nitrate), Cas VII-gly (1,10-phenanthroline glycinato copper(II) nitrate), and Cas IX-gly (2,2'-bipyridine glycinato copper(II) nitrate)} and of a Casiopeínas® with a different co-ligand (Cas III-Cs; 4,7-dimethyl-1,10-phenanthroline salicylaldehydato-copper(II) nitrate). While all of them produce DNA degradation, the performance in the presence of a radical scavenger suggests the existence of differences in their mechanism of interaction with DNA.
authors.affiliation: Laboratorio de Interacciones Moleculares, Facultad de Ciencias, Universidad de la Repùblica, Iguá 4225, 11400, Montevideo, Uruguay.
authors.forename: Lorena
authors.initials: L
authors.lastname: Becco
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: García-Ramos
authors.forename: Lena Ruiz
authors.initials: LR
authors.lastname: Azuara
authors.forename: Dinorah
authors.initials: D
authors.lastname: Gambino
authors.forename: Beatriz
authors.initials: B
authors.lastname: Garat
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; C505569:casiopeina II-glycine; D003300:Copper; D004247:DNA