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@article{792858,
author = {Kašpárková, Jana and Marini Palomeque, María Victoria and Najajreh, Yousef and Gibson, Dan and Brabec, Viktor},
article_location = {Washington, USA},
article_number = {20},
keywords = {platinum complexes; DNA; anticancer},
language = {eng},
issn = {0006-2960},
journal = {Biochemistry},
title = {DNA Binding Mode of the Cis and Trans Geometries of New Antitumor Nonclassical Platinum Complexes Containing Piperidine, Piperazine, or 4-Picoline Ligand in Cell-Free Media. Relations to Their Activity in Cancer Cell Lines},
volume = {42},
year = {2003}
}
TY - JOUR
ID - 792858
AU - Kašpárková, Jana - Marini Palomeque, María Victoria - Najajreh, Yousef - Gibson, Dan - Brabec, Viktor
PY - 2003
TI - DNA Binding Mode of the Cis and Trans Geometries of New Antitumor Nonclassical Platinum Complexes Containing Piperidine, Piperazine, or 4-Picoline Ligand in Cell-Free Media. Relations to Their Activity in Cancer Cell Lines
JF - Biochemistry
VL - 42
IS - 20
SP - 6321 -6332
EP - 6321 -6332
PB - American Chemical Society
SN - 00062960
KW - platinum complexes
KW - DNA
KW - anticancer
N2 - The global modification of mammalian and plasmid DNAs by novel platinum compounds, cis- or trans-[PtCl2(NH3)(Am)], where Am = NH3, nonplanar heterocycle piperidine, piperazine, or aromatic planar heterocycle 4-picoline, was investigated in cell-free media using various biochemical and biophysical methods. These modifications have been compared with the activity of these new compounds in several tumor cell lines including those resistant to antitumor cis-diamminedichloroplatinum(II) (cisplatin). The results show that the replacement of the NH3 group in cisplatin by the heterocyclic ligands does not considerably affect the DNA binding mode of this drug. Cytotoxicity studies have revealed that the replacement lowers the activity of the platinum compound in both sensitive and resistant cell lines. It has been suggested that the reduced activity of these analogues of cisplatin is associated with some features of the damaged DNA and/or its cellular processing. Alternatively, the reduced activity of the analogues of cisplatin might also be due to the factors that do not operate directly at the level of the target DNA, such as intracellular platinum uptake. In contrast to the analogues of cisplatin, the replacement of one ammine group by the heterocyclic ligand in its clinically ineffective trans isomer (transplatin) results in a radical enhancement of its activity in tumor cell lines. Importantly, this replacement also markedly alters the DNA binding mode of transplatin. The results support the view that one strategy of how to activate the trans geometry in bifunctional platinum(II) compounds including circumvention of resistance to cisplatin may consist of a chemical modification of the ineffective transplatin that results in an increased stability of its intrastrand cross-links in double-helical DNA and/or in an increased efficiency to form interstrand cross-links.
ER -
KAŠPÁRKOVÁ, Jana, María Victoria MARINI PALOMEQUE, Yousef NAJAJREH, Dan GIBSON and Viktor BRABEC. DNA Binding Mode of the Cis and Trans Geometries of New Antitumor Nonclassical Platinum Complexes Containing Piperidine, Piperazine, or 4-Picoline Ligand in Cell-Free Media. Relations to Their Activity in Cancer Cell Lines. \textit{Biochemistry}. Washington, USA: American Chemical Society, 2003, vol.~42, No~20, p.~6321 -6332. ISSN~0006-2960.
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