Synthesis and in vitro Anticancer Activity of Octahedral Platinum(IV) Complexes with Cyclohexyl‐Functionalized Ethylenediamine‐N,N′‐Diacetate‐Type Ligands

• DOI: 10.1002/cmdc.201000058
• Publication Date: 2010-04-20T17:52:38Z
• Authors: Jelena M. Lazić; Ljubica Vučićević; Sanja Grgurić‐Šipka; Kristina Janjetović; Goran N. Kaluđerović; Maja Misirkić; Maja Gruden‐Pavlović; Dušan Popadić; Reinhard Paschke; Vladimir Trajković; Tibor J. Sabo
• Keywords: Viability assay; Ethylene diamine

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 density functional theory analysis revealed that s-cis is preferred geometry these tetradentate-coordinated (S,S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoate. viability cancer cell lines (U251 human glioma, C6 rat L929 mouse fibrosarcoma, B16 melanoma) was assessed by measuring mitochondrial dehydrogenase lactate release. Cell-cycle distribution, oxidative stress, caspase activation, induction autophagy were analyzed flow cytometry using appropriate fluorescent reporter dyes. cytotoxic against various (IC(50) range: 1.9-8.7 microM) higher than cisplatin 10.9-67.0 proceeded through completely different mechanisms. Cisplatin induced caspase-dependent apoptosis associated cytoprotective autophagic response. In contrast, new caused rapid, caspase-independent, stress-mediated non-apoptotic death characterized massive cytoplasmic vacuolization, membrane damage, absence protective autophagy.