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

Eurobic9, 2-6 September, 2008, Wrocław, Poland
P45. Complexes of Triazole Derivatives with Copper(II).
Study of DNA Damage and HDV Ribozyme Activity Inhibition
M. Dziuba a , J. Wrzesiński b , J. Ciesiołka b , W. Szczepanik a , L. Z. Ciunik a , M. Barys a
and M. Jeżowska-Bojczuk a
a
Faculty of Chemistry, University of Wroclaw, F. Joliot-Curie 14, 50-383 Wroclaw,
e-mail: magdadz@eto.wchuwr.pl
b
Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznań, Poland
1, 2, 4-triazoles and their derivatives are very interesting compounds due to their role in medicinal, agricultural
and industrial fields. They were proved to reveal anti-cancer, anti-fungal and anti-inflammatory activity [1-3].
We have studied a number of novel chiral 1, 2, 4-triazole derivatives (i.e. 4-amino-1, 2, 4-triazol-2, 4dinitrobenzaldehyde
(2, 4dnbald), 4-amino-1, 2, 4-triazol-2-nitrobenzaldehyde (2nbald), 4-amino-1, 2, 4-triazol-
3-nitrobenzaldehyde (3nbald) and 4-amino-1, 2, 4-triazol-4-nitro- benzaldehyde (4nbald)). The newly
synthesized compounds were active against bacteria and fungi [4]. Ligands alone, as well as their copper
complexes were also examined for their ability to interact with both RNA and DNA.
The studied derivatives showed relatively weak inhibitory properties towards cleavage of antigenomic delta
ribozyme. However, their Cu 2+ complexes reduced ribozyme cleavage kinetics by a factor of 2 - 3.5 in
comparison to the uncomplexed compounds. The strongest effect with 2nbald and 2, 4-dnbald-Cu 2+ complex for
Mg 2+ or Mn 2+ -promoted cleavage was observed, respectively. Chemical probing showed preferential binding of
the complexes to the J4/2 region of HDV ribozyme. Our results suggest that RNA molecules are potential targets
for binding of triazole-Cu 2+ complexes [5].
Metal complexes of various bioavailable ligands and xenobiotics are known to induce cleavage of DNA. We
studied pBluescriptSK+ plasmid damage caused by the Cu 2+ -nbald species. We observed rather weak influence
of Cu 2+ -nbald complexes on nucleic acid reflected by a moderate amount of single strand nicks. Only Cu 2+ -2,
4dnbald in presence of H2O2 was able to induce the double strand scission of plasmid DNA.
References:
[1] M.C. Hosur, M.B. Talawar, R.S. Bennur, S.C. Bennur and P.A. Patil, Indian J. Pharm. Sci 55, 86 (1993)
[2] Y.S. Wu, H.K. Lee, S.F.Y., Li, J. Chromatogr. A 912, 171 (2001)
[3] D.R. Williams, Chem. Rev. 72, 203 (1972)
[4] M. Barys, Z. Ciunik data not published
[5] J. Wrzesiński, M. Dziuba, J. Ciesiołka, W. Szczepanik, M. Jeżowska-Bojczuk submitted
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