ISBN: 978-83-60043-10-3 - eurobic9

Eurobic9, 2-6 September, 2008, Wrocław, Poland
P7. Structural features and oxidative stress towards plasmid DNA of
apramycin copper complex
D. Balenci a , G. Bonechi a , N. D’Amelio a , E. Gaggelli a , N. Gaggelli a , E. Molteni a ,
G. Valensin a , W. Szczepanik b , M. Dziuba b , J. Skała c and M. Jeżowska-Bojczuk b
a Department of Chemistry, University of Siena, Via Aldo Moro, 53100 Siena, Italy
b Faculty of Chemistry, University of Wrocław, F. Joliot-Curie 14, Wrocław, 50-383, Poland
c Microbiological Institute, University of Wrocław, Przybyszewskiego 63, 51-148, Wrocław,
Poland
Apramycin is an aminocyclitol antibiotic belonging to the aminoglycoside family. It contains a bicyclic
aminooctodiosyl sugar, which is the only substituent of the 2-deoxystreptamine (2-DOS) moiety, at the 4
position. Apramycin is unique among aminoglycosides both for its molecular structure and for its mode of
action, inhibiting the elongation by blocking the ribosome translocation. The mechanism underlying its
pharmacological effects has been extensively studied, showing that this antibiotic strongly interacts with the A
site in 16S rRNA. First isolated from Streptomyces tenebrarius, apramycin is used to treat infections caused by
Gram-negative bacteria.
Toxicological pattern of apramycin as well as other aminoglycosides has not been fully understood. Some
evidence has been collected suggesting that toxicological effects of aminoglycosidic antibiotics could be
connected to the catalytic action exerted by copper ions [1, 2]. Copper complexes of several aminoglycosides
induce oxidative stress towards nucleic acids, through formation of reactive oxygen species by the redox active
metal center [3]. In vivo cleavage of DNA and RNA by copper aminoglycosides has been observed [4].
Copper(II) complexes of aminoglycosides have been extensively studied by spectroscopic and potentiometric
techniques, and they were found to be the strongest with respect to complexes with different metal ions [5, 6].
The frequent occurrence of vicinal amine and hydroxyl groups in such antibiotics constitutes a potential metalchelating
motif; the resulting chelates are more stable than the monodentate one. All mentioned aminoglycosides
bind copper by deprotonated amino groups and/or deprotonated hydroxyl groups, depending on the pH value.
This study is aimed at reporting the interaction of apramycin with copper(II) ions, which has not been
characterized up to now, defining also a structural model of the obtained complex at nearly physiological pH. A
second goal is devoted to show the effects of apramycin-Cu(II) complex on plasmid DNA.
Acknowledgements: We acknowledge the MIUR (FIRB RBNE03PX83_003) and the C.I.R.M.M.P. (Consorzio
Interuniversitario Risonanze Magnetiche di Metalloproteine Paramagnetiche) for financial support.
References:
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269, 5547 (2002)
[2] W. Szczepanik, J. Ciesiołka, J. Wrzesiński, J. Skała and M. Jeżowska-Bojczuk, Dalton Trans., 1488 (2003)
[3] A. Patwardhan and J.A.Cowan, Chem.Commun., 1490 (2001)
[4] C.A. Chen, J.A. Cowan, Chem. Commun., 196 (2002)
[5] N. D’Amelio, E. Gaggelli, N. Gaggelli, E. Molteni, M.C. Baratto, G. Valensin, M. Jeżowska-Bojczuk, W.
Szczepanik, Dalton Trans., 363 (2004)
[6] W. Szczepanik, A. Czarny, E. Zaczyńska and M. Jeżowska-Bojczuk, J. Inorg. Biochem. 98, 245 (2004)
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