Synthesis and in vitro Anticancer Activity of Octahedral Platinum(IV) Complexes with Cyclohexyl-Functionalized Ethylenediamine-N,N '-Diacetate-Type Ligands
Samo za registrovane korisnike
2010
Autori
Lazić, Jelena M.Vucicevic, Ljubica

Grgurić-Šipka, Sanja

Janjetovic, Kristina

Kaluđerović, Goran N.

Misirkic, Maja
Gruden-Pavlović, Maja

Popadić, Dušan

Paschke, Reinhard
Trajković, Vladimir S.

Sabo, Tibor

Članak u časopisu (Objavljena verzija)

Metapodaci
Prikaz svih podataka o dokumentuApstrakt
The present study describes the synthesis and anticancer activity of novel octahedral Pt-IV complexes with cyclohexyl functionalized ethylenediamine-N,N'-diacetate-type ligands. Molecular mechanics calculations and density functional theory analysis revealed that s-cis is the preferred geometry of these Pt-IV complexes with tetradentate-coordinated (S,S)-ethylenediamineN,N'-di-2-(3-cyclohexyl)propanoate. The viability of cancer cell lines (U251 human glioma, C6 rat glioma, L929 mouse fibrosarcoma, and B16 human melanoma) was assessed by measuring mitochondrial dehydrogenase activity and lactate dehydrogenase release. Cell-cycle distribution, oxidative stress, caspase activation, and induction of autophagy were analyzed by flow cytometry using appropriate fluorescent reporter dyes. The cytotoxic activity of novel Pt-IV complexes against various cancer cell lines (IC50 range: 1.9-8.7 mu m) was higher than that of cisplatin (IC50 range: 10.9-67.0 mu m) and proceeded through completely dif...ferent mechanisms. Cisplatin induced caspase-dependent apoptosis associated with the cytoprotective autophagic response. In contrast, the new Pt-IV complexes caused rapid, caspase-independent, oxidative stress-mediated non-apoptotic cell death characterized by massive cytoplasmic vacuolization, cell membrane damage, and the absence of protective autophagy.
Ključne reči:
apoptosis / autophagy / cancer / oxidative stress / platinumIzvor:
ChemMedChem, 2010, 5, 6, 881-889Izdavač:
- Wiley-V C H Verlag Gmbh, Weinheim
Projekti:
- Sinteza, karakterizacija i aktivnost organskih i koordinacionih jedinjenja i njihova primena u (bio)nanotehnologiji (RS-142010)
- Citotoksični, citoprotektivni i imunomodulatorni efekti nanočestica (RS-145073)
DOI: 10.1002/cmdc.201000058
ISSN: 1860-7179
PubMed: 20408161