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

Eurobic9, 2-6 September, 2008, Wrocław, Poland
P74. Cytotoxic Properties, DNA and Glutathion Interactions of New
Lipophilic trans-platinum Complexes Tethered to 1-adamantylamine
A. Halamikova a , P. Heringova a , J. Kasparkova a , V. Brabec a , G. Natile b
a
Institute of biophysics ASCR, Kralovopolska 135, CZ-612-65, Brno, Czech Republic
e-mail: halamikova@ibp.cz
b
Department of Pharmaceutical Chemistry, University of Bari, , I-70125, Bari, Italy
Platinum-based anticancer compounds are a clinically successful group of therapeutic agents. In spite of the fact
that they belong to the world’s best selling anticancer drugs, their use is constrained by dose-limiting side-effects
and the problem of acquired resistance. To avoid these problems, for over three decades, continuous efforts have
been made with a primary focus on the development of new platinum drugs and mechanisms underlying their
antitumor effects.
Cytotoxicity and mutagenicity of new platinum complexes trans, trans, trans-[PtCl2(CH3COO)2(NH3)(1adamantylamine)]
and its reduced analog trans-[PtCl2(NH3)(1-adamantylamine)] were examined. In addition,
several factors underlying biological effects of these trans-platinum complexes, such as drug accumulation in
cells, DNA binding and deactivation of complexes by sulfur-containing compounds, using various biochemical
methods were investigated.
A notable feature of the growth inhibition assays using human cancer cell lines was the remarkable
circumvention of both acquired and intrinsic resistance of conventional cisplatin by the two new lipophilic transplatinum
compounds. The results also suggest that the pharmacological factors, such as enhanced accumulation
of the drug in cells, altered DNA binding mode and deactivation of the trans-[PtCl2(NH3)(1-adamantylamine)]
by glutathione, are likely to play a significant role in the mechanism of the biological action of these new transplatinum
complexes.
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