| PROKOP, Radim, Jana KAŠPÁRKOVÁ, Olga NOVAKOVA, María Victoria MARINI PALOMEQUE, Ana M. PIZARRO, Carmen NAVARRO-RANNINGER a Viktor BRABEC. DNA interactions of new antitumor platinum complexes with trans geometry activated by a 2-metylbutylamine or sec-butylamine ligand. Biochemical Pharmacology. Oxford, UK: Elsevier, 2004, roč. 67, č. 6, s. 1097-109, 13 s. ISSN 0006-2952. |
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@article{792965,
author = {Prokop, Radim and Kašpárková, Jana and Novakova, Olga and Marini Palomeque, María Victoria and Pizarro, Ana M. and NavarroandRanninger, Carmen and Brabec, Viktor},
article_location = {Oxford, UK},
article_number = {6},
keywords = {cisplatin; platinum complexes; DNA; antitumor},
language = {eng},
issn = {0006-2952},
journal = {Biochemical Pharmacology},
title = {DNA interactions of new antitumor platinum complexes with trans geometry activated by a 2-metylbutylamine or sec-butylamine ligand.},
volume = {67},
year = {2004}
}
TY - JOUR
ID - 792965
AU - Prokop, Radim - Kašpárková, Jana - Novakova, Olga - Marini Palomeque, María Victoria - Pizarro, Ana M. - Navarro-Ranninger, Carmen - Brabec, Viktor
PY - 2004
TI - DNA interactions of new antitumor platinum complexes with trans geometry activated by a 2-metylbutylamine or sec-butylamine ligand.
JF - Biochemical Pharmacology
VL - 67
IS - 6
SP - 1097-109
EP - 1097-109
PB - Elsevier
SN - 00062952
KW - cisplatin
KW - platinum complexes
KW - DNA
KW - antitumor
N2 - The global modification of mammalian and plasmid DNAs by novel platinum compounds, trans-[PtCl(2)(NH(3))(Am)], where Am=2 -methylbutylamine or sec-butylamine was investigated in cell-free media using various biochemical and biophysical methods. These modifications were analyzed in the context of the activity of these new compounds in several tumor cell lines including those resistant to antitumor cis-diamminedichloroplatinum(II) (cisplatin). The results showed that the replacement of one amine group by 2-methylbutylamine or sec-butylamine ligand in clinically ineffective trans-diamminedichloroplatinum(II) (transplatin) resulted in a radical enhancement of its activity in tumor cell lines so that they are more cytotoxic than cisplatin and exhibited significant antitumor activity including activity in cisplatin-resistant tumor cells. Importantly, this replacement also markedly altered DNA binding mode of transplatin and reduced the efficiency of repair systems to remove the adducts of the new analogues from DNA. The results support the view that one strategy to activate trans geometry in bifunctional platinum(II) compounds including circumvention of resistance to cisplatin may consist in a chemical modification of the ineffective transplatin which results in an increased efficiency to form DNA interstrand cross-links.
ER -
PROKOP, Radim, Jana KAŠPÁRKOVÁ, Olga NOVAKOVA, María Victoria MARINI PALOMEQUE, Ana M. PIZARRO, Carmen NAVARRO-RANNINGER a Viktor BRABEC. DNA interactions of new antitumor platinum complexes with trans geometry activated by a 2-metylbutylamine or sec-butylamine ligand. \textit{Biochemical Pharmacology}. Oxford, UK: Elsevier, 2004, roč.~67, č.~6, s.~1097-109, 13 s. ISSN~0006-2952.
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