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

0126967 - BFU-R 20033048 RIV US eng J - Journal Article
Kašpárková, Jana - Marini, Victoria - Najajreh, Y. - Gibson, D. - Brabec, Viktor
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.
Biochemistry. Roč. 42, č. 20 (2003), s. 6321-6332. ISSN 0006-2960
R&D Projects: GA AV ČR IAA5004101; GA AV ČR KJB5004301; GA ČR GA305/01/0418
Institutional research plan: CEZ:AV0Z5004920
Keywords : cross links * DNA * nonclassical platinum complexes
Subject RIV: BO - Biophysics
Impact factor: 3.922, year: 2003

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. These modifications have been compared with the activity of these new compounds in several tumor cell lines. 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. 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. This replacement also markedly alters the DNA binding mode of transplatin.
Permanent Link: http://hdl.handle.net/11104/0025194