RT Journal Article
SR Electronic
T1 DNA Modifications by Antitumor<em>trans</em>-[PtCl<sub>2</sub>(<em>E</em>-Iminoether)<sub>2</sub>]
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 354
OP 361
DO 10.1124/mol.52.3.354
VO 52
IS 3
A1 Renata Žaludová
A1 Alena Žákovská
A1 Jana Kašpárkova
A1 Zdenka Balcarová
A1 Oldřich Vrána
A1 Mauro Coluccia
A1 Giovanni Natile
A1 Viktor Brabec
YR 1997
UL http://molpharm.aspetjournals.org/content/52/3/354.abstract
AB Recent findings that an analogue of clinically ineffective transplatin,trans-[PtCl2(E-iminoether)2], exhibits antitumor activity has helped reevaluation of the empirical structure-antitumor activity relationship generally accepted for platinum(II) complexes. According to this relationship, only thecis geometry of leaving ligands in the bifunctional platinum(II) complexes, should be therapeutically active. Global modifications of natural DNAs in cell-free media bytrans-[PtCl2(E-iminoether)2] were studied through various molecular biophysical methods and compared with modifications bycis-[PtCl2(E-iminoether)2], transplatin, cisplatin, and monofunctional chlorodiethylenetriamineplatinum(II) chloride. Thus, the results of this study have extended our recent finding, indicating that the prevalent lesion occurring in double-helical DNA on its modification bytrans-[PtCl2(E-iminoether)2] is a monofunctional adduct at guanine residues. The modification bytrans-[PtCl2(E-iminoether)2] has been found to induce local distortions in DNA, which have a character differing fundamentally from those induced by both clinically ineffective or antitumor platinum complexes tested in this study. The different character of alterations induced in DNA by the adducts oftrans-[PtCl2(E-iminoether)2] and transplatin has been suggested to be relevant to the unexpected observation that the new complex with leaving chloride groups intrans position exhibits antitumor efficacy. In addition, the results support the idea that platinum drugs that bind to DNA in a manner fundamentally different from that of cisplatin can exhibit altered biological properties, including differing spectra and intensities of antitumor activity.