Toxicity in tumor cells, DNA binding mode, and resistance to decomposition by sulfur nucleophiles of new dinuclear bifunctional trans-Pt-II complexes containing long alkane linkers

0392664 - BFÚ 2014 RIV US eng J - Článek v odborném periodiku
Prachařová, J. - Nováková, Olga - Kašpárková, Jana - Gibson, J. - Brabec, Viktor
Toxicity in tumor cells, DNA binding mode, and resistance to decomposition by sulfur nucleophiles of new dinuclear bifunctional trans-Pt-II complexes containing long alkane linkers.
Pure and Applied Chemistry. Roč. 85, č. 2 (2013), s. 343-354. ISSN 0033-4545. E-ISSN 1365-3075
Grant CEP: GA ČR(CZ) GD301/09/H004
Institucionální podpora: RVO:68081707
Klíčová slova: PLATINUM ANTITUMOR COMPLEXES * INTERSTRAND CROSS-LINKS * GEOMETRIC ISOMERISM
Kód oboru RIV: BO - Biofyzika
Impakt faktor: 3.112, rok: 2013

In an effort to design dinuclear Pt-II compounds that maintain the target (DNA) binding profile of the trans-oriented dinuclear bifunctional Pt-II complexes containing aliphatic linker chains but are less susceptible to metabolic decomposition, the new, long-chain dinuclear Pt-II complexes-[{trans-PtCl(dien)}(2)-mu-(CH2)(n)](2+) (n = 7,10,12, dien = diethylenetriamine)-were synthesized. The toxicity of these metallodrugs was examined in ovarian tumor cell lines. The results showed that the activity of these complexes increased with growing length of the linker; the activity of complex containing the longest linker (n = 12) was comparable with that of cis-diamminedichloridoplatinum(II) (cisplatin). This observation correlated with the results of DNA binding studies performed in cell-free media. The results of these studies demonstrated that the growing length of the aliphatic bridge promoted more distorting conformational alterations induced in DNA. Attention was also paid to the reactivity of {[Pt(dien)Cl](2)-alkane} compounds with glutathione (GSH).
Trvalý link: http://hdl.handle.net/11104/0221495