| Synthesis and in vitro anticancer activity of octahedral platinum(IV) complexes with cyclohexyl-functionalized ethylenediamine-N,N'-diacetate-type ligands. | |
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MedLine Citation:
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PMID: 20408161 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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)-ethylenediamine-N,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 (IC(50) range: 1.9-8.7 microM) was higher than that of cisplatin (IC(50) range: 10.9-67.0 microM) and proceeded through completely different 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. |
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Authors:
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Jelena M Lazić; Ljubica Vucićević; Sanja Grgurić-Sipka; Kristina Janjetović; Goran N Kaluderović; Maja Misirkić; Maja Gruden-Pavlović; Dusan Popadić; Reinhard Paschke; Vladimir Trajković; Tibor J Sabo |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: ChemMedChem Volume: 5 ISSN: 1860-7187 ISO Abbreviation: ChemMedChem Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-06-07 Completed Date: 2010-09-10 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101259013 Medline TA: ChemMedChem Country: Germany |
Other Details:
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Languages: eng Pagination: 881-9 Citation Subset: IM |
Affiliation:
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Faculty of Chemistry, University of Belgrade, Studentski trg 12-16, 11000 Belgrade, Serbia. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antineoplastic Agents / chemical synthesis*, chemistry, toxicity Apoptosis Cell Line, Tumor Cisplatin / pharmacology Coordination Complexes / chemical synthesis*, chemistry, toxicity Ethylenediamines / chemistry* Humans Ligands Mice Platinum / chemistry* Rats |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Coordination Complexes; 0/Ethylenediamines; 0/Ligands; 107-15-3/ethylenediamine; 15663-27-1/Cisplatin; 7440-06-4/Platinum |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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