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Synthesis and in vitro Anticancer Activity of Octahedral Platinum(IV) Complexes with Cyclohexyl-Functionalized Ethylenediamine-N,N '-Diacetate-Type Ligands
dc.creator | Lazić, Jelena | |
dc.creator | Vucicevic, Ljubica | |
dc.creator | Grgurić-Šipka, Sanja | |
dc.creator | Janjetovic, Kristina | |
dc.creator | Kaluđerović, Goran N. | |
dc.creator | Misirkic, Maja | |
dc.creator | Gruden-Pavlović, Maja | |
dc.creator | Popadić, Dušan | |
dc.creator | Paschke, Reinhard | |
dc.creator | Trajković, Vladimir S. | |
dc.creator | Sabo, Tibor | |
dc.date.accessioned | 2018-11-22T00:16:32Z | |
dc.date.available | 2018-11-22T00:16:32Z | |
dc.date.issued | 2010 | |
dc.identifier.issn | 1860-7179 | |
dc.identifier.uri | https://cherry.chem.bg.ac.rs/handle/123456789/1088 | |
dc.description.abstract | 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 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. | en |
dc.publisher | Wiley-V C H Verlag Gmbh, Weinheim | |
dc.relation | info:eu-repo/grantAgreement/MESTD/MPN2006-2010/142010/RS// | |
dc.relation | info:eu-repo/grantAgreement/MESTD/MPN2006-2010/145073/RS// | |
dc.rights | restrictedAccess | |
dc.source | ChemMedChem | |
dc.subject | apoptosis | en |
dc.subject | autophagy | en |
dc.subject | cancer | en |
dc.subject | oxidative stress | en |
dc.subject | platinum | en |
dc.title | Synthesis and in vitro Anticancer Activity of Octahedral Platinum(IV) Complexes with Cyclohexyl-Functionalized Ethylenediamine-N,N '-Diacetate-Type Ligands | en |
dc.type | article | |
dc.rights.license | ARR | |
dcterms.abstract | Јањетовиц, Кристина; Вуцицевиц, Љубица; Пасцхке, Реинхард; Трајковиц, Владимир; Сабо, Тибор; Груден-Павловић, Маја; Калудеровиц, Горан Н.; Гргурић-Шипка, Сања; Лазиц, Јелена М.; Попадиц, Дусан; Мисиркиц, Маја; | |
dc.citation.volume | 5 | |
dc.citation.issue | 6 | |
dc.citation.spage | 881 | |
dc.citation.epage | 889 | |
dc.identifier.wos | 000278969200010 | |
dc.identifier.doi | 10.1002/cmdc.201000058 | |
dc.citation.other | 5(6): 881-889 | |
dc.citation.rank | M21 | |
dc.identifier.pmid | 20408161 | |
dc.type.version | publishedVersion | en |
dc.identifier.scopus | 2-s2.0-77953095723 |