Cu(Nor)2·5H2O, a complex of Cu(II) with Norfloxacin: theoretic approach and biological studies. Cytotoxicity and genotoxicity in cell cultures

ANA LAURA DI VIRGILIO; IGNACIO LEÓN; CARLOS A. FRANCA; ISABEL HENAO; GLORIA TOBÓN; SUSANA B. ETCHEVERRY

MOLECULAR AND CELLULAR BIOCHEMISTRY

SPRINGER

Lugar: Berlin; Año: 2012 p. 53 - 61

0300-8177

Abstract Norfloxacin is a fluoroquinolone antibiotic usedin the treatment of bacterial infections. In this article, westudied the potential antitumoral action of a complex ofNorfloxacin with Cu(II), Cu(Nor)25H2O on osteosarcomacells (UMR106) and calvaria-derived cells (MC3T3-E1),evaluating its cytotoxicity and genitoxicity. We have alsoelucidated the more stable conformation of this complexunder physiologic conditions by Molecular Dynamic simulationsbased on the model of the canonical ensemble andPM6 force field. When solvent effect was taken into account,the complex conformation with both carbonyl groups inopposite sides displayed lower energy. Cu(Nor)25H2Ocaused an inhibitory effect on the proliferation on both celllines from 300 lM (P\0.01). Nevertheless, the decline oncell proliferation of UMR106 cells was more pronounced(45 % vs basal) than in MC3T3-E1 cells (20 % vs basal) at300 lM (P\0.01). Cu(Nor)25H2O altered lysosomalmetabolism (Neutral Red assay) in a dose-dependent mannerfrom 300 lM (P\0.001). Morphological studies showedimportant transformations that correlated with a decrease inthe number of cells in a dose-dependent manner. Moreover,Cu(Nor)25H2O caused statistically significant genotoxiceffects on both osteoblast cell lines in a lower range ofconcentrations (Micronucleus assay) (P\0.05 at 10 lM,P\0.001 from 25 to 50 lM). UMR106 cells displayed adose-related genotoxic effect between 5 and 25 lM whilethe MC3T3-E1 cells showed a narrower concentrationdependent range. Altogether, these results suggest thatCu(Nor)25H2O is a good candidate to be further evaluatedfor alternative therapeutics in cancer treatment.