DNA and RNA damage by Cu(II)‐amikacin complex

Abstract

The oxidation-promoting reactivity of copper(II) complex of aminoglycosidic antibiotic amikacin [Cu(II)-Ami] in the presence of hydrogen peroxide, was studied at pH 7.4, using 2¢-deoxyguanosine (dG), pBR322 plasmid DNA and yeast tRNA Phe as target molecules. The mixtures of complex with H 2 O 2 were found to be efficient oxidants, converting dG to its 8-oxo derivative, generating strand breaks in plasmid DNA and multiple cleavages in tRNA Phe . The complex underwent autooxidation as well, with amikacin hydroperoxides as likely major products. This reactivity pattern was found to be due to a combination of metal-bound and free hydroxyl radicals.

Preferences of kanamycin A towards copper(II). Effect of the resulting complexes on immunological mediators production by human leukocytes

“…These data justify our previous study on copper chelation by aminoglycosides [27][28][29] and the reactivity of the formed complexes [4,5]. They may also support the idea that this metal ion is rightly suspected to take part in the chemical basis of aminoglycosides induced toxic effects [7][8][9].…”

“…This particular activity was also tested towards oxidation susceptible biomolecules. The obtained results have shown that the cupric complexes of aminoglycosides have potency to convert a nucleoside 2 0 -deoxyguanosine into its 8-oxo derivative, as well as bring about damage to plasmid DNA and tRNA [6][7][8][9]. Our studies suggest that these antibiotics, following Cu(II) ions complexation, may be suspected of genotoxic properties.…”

“…At pH 7.4 only 5% of metal content stays bound to kA, while the rest constitutes Cu(II)-DAHKam complexes. Such vestigial appearance of species, however, cannot diminish their possible biological role due to their reactivity promoting hydroxyl radicals formation [4][5][6][7][8][9]. Although DAHK has appeared recently not to be a reliable thermodynamic model system of HSA, it was affirmed that they bind cupric ions distinctly stronger than albumins [30].…”

Identification of copper(II) binding sites in actinomycin D, a cytostatic drug – correlation of coordination with DNA damage

“…Our experience in studies of Cu(II) interactions with various antibiotics: tetracyclines [19], lincosamides [20,21], aminoglycosides [22][23][24][25][26][27] and an antiviral agent -1-deoxynojirimycin [28] prompted us to undertake the study on the Cu(II) chelation by AD and the impact of this binding on AD-related DNA damage processes.…”

FeS-Induced Radical Formation and Its Effect on Plasmid DNA

“…1). During electrophoresis, supercoiled forms move more easily through the gel and are separated from the relaxed circular forms (Jezowska-Bojczuk et al 2002;Rozenberg-Arska et al 1985;Toyokuni and Sagripanti 1992). Plasmids are therefore widely used as test molecules in studies of nucleic acid chemistry, since their behavior during reactions is readily traceable.…”