Synthesis and in vitro Anticancer Activity of Octahedral Platinum(IV) Complexes with Cyclohexyl-Functionalized Ethylenediamine-N,N '-Diacetate-Type Ligands
Само за регистроване кориснике
2010
Аутори
Lazić, JelenaVucicevic, Ljubica
Grgurić-Šipka, Sanja
Janjetovic, Kristina
Kaluđerović, Goran N.
Misirkic, Maja
Gruden-Pavlović, Maja
Popadić, Dušan
Paschke, Reinhard
Trajković, Vladimir S.
Sabo, Tibor
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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.
Кључне речи:
apoptosis / autophagy / cancer / oxidative stress / platinumИзвор:
ChemMedChem, 2010, 5, 6, 881-889Издавач:
- Wiley-V C H Verlag Gmbh, Weinheim
Финансирање / пројекти:
- Синтеза, карактеризација и активност органских и координационих једињења и њихова примена у (био)нанотехнологији (RS-MESTD-MPN2006-2010-142010)
- Цитотоксични, цитопротективни и имуномодулаторни ефекти наночестица (RS-MESTD-MPN2006-2010-145073)
DOI: 10.1002/cmdc.201000058
ISSN: 1860-7179
PubMed: 20408161
WoS: 000278969200010
Scopus: 2-s2.0-77953095723
Колекције
Институција/група
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Lazić, Jelena AU - Vucicevic, Ljubica AU - Grgurić-Šipka, Sanja AU - Janjetovic, Kristina AU - Kaluđerović, Goran N. AU - Misirkic, Maja AU - Gruden-Pavlović, Maja AU - Popadić, Dušan AU - Paschke, Reinhard AU - Trajković, Vladimir S. AU - Sabo, Tibor PY - 2010 UR - https://cherry.chem.bg.ac.rs/handle/123456789/1088 AB - 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. PB - Wiley-V C H Verlag Gmbh, Weinheim T2 - ChemMedChem T1 - Synthesis and in vitro Anticancer Activity of Octahedral Platinum(IV) Complexes with Cyclohexyl-Functionalized Ethylenediamine-N,N '-Diacetate-Type Ligands VL - 5 IS - 6 SP - 881 EP - 889 DO - 10.1002/cmdc.201000058 ER -
@article{ author = "Lazić, Jelena and Vucicevic, Ljubica and Grgurić-Šipka, Sanja and Janjetovic, Kristina and Kaluđerović, Goran N. and Misirkic, Maja and Gruden-Pavlović, Maja and Popadić, Dušan and Paschke, Reinhard and Trajković, Vladimir S. and Sabo, Tibor", year = "2010", 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.", publisher = "Wiley-V C H Verlag Gmbh, Weinheim", journal = "ChemMedChem", title = "Synthesis and in vitro Anticancer Activity of Octahedral Platinum(IV) Complexes with Cyclohexyl-Functionalized Ethylenediamine-N,N '-Diacetate-Type Ligands", volume = "5", number = "6", pages = "881-889", doi = "10.1002/cmdc.201000058" }
Lazić, J., Vucicevic, L., Grgurić-Šipka, S., Janjetovic, K., Kaluđerović, G. N., Misirkic, M., Gruden-Pavlović, M., Popadić, D., Paschke, R., Trajković, V. S.,& Sabo, T.. (2010). Synthesis and in vitro Anticancer Activity of Octahedral Platinum(IV) Complexes with Cyclohexyl-Functionalized Ethylenediamine-N,N '-Diacetate-Type Ligands. in ChemMedChem Wiley-V C H Verlag Gmbh, Weinheim., 5(6), 881-889. https://doi.org/10.1002/cmdc.201000058
Lazić J, Vucicevic L, Grgurić-Šipka S, Janjetovic K, Kaluđerović GN, Misirkic M, Gruden-Pavlović M, Popadić D, Paschke R, Trajković VS, Sabo T. Synthesis and in vitro Anticancer Activity of Octahedral Platinum(IV) Complexes with Cyclohexyl-Functionalized Ethylenediamine-N,N '-Diacetate-Type Ligands. in ChemMedChem. 2010;5(6):881-889. doi:10.1002/cmdc.201000058 .
Lazić, Jelena, Vucicevic, Ljubica, Grgurić-Šipka, Sanja, Janjetovic, Kristina, Kaluđerović, Goran N., Misirkic, Maja, Gruden-Pavlović, Maja, Popadić, Dušan, Paschke, Reinhard, Trajković, Vladimir S., Sabo, Tibor, "Synthesis and in vitro Anticancer Activity of Octahedral Platinum(IV) Complexes with Cyclohexyl-Functionalized Ethylenediamine-N,N '-Diacetate-Type Ligands" in ChemMedChem, 5, no. 6 (2010):881-889, https://doi.org/10.1002/cmdc.201000058 . .