Ni(II) complex with bishydrazone ligand: synthesis, characterization, DNA binding studies and pro-apoptotic and pro-differentiation induction in human cancerous cell lines
2016
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Аутори
Filipović, Nenad R.Bjelogrlić, Snežana
Todorović, Tamara R.
Blagojević, Vladimir A.
Muller, Christian D.
Marinković, Aleksandar
Vujcić, Miroslava
Janović, Barbara
Malesević, Aleksandar
Begović, Nebojša
Sencanski, Milan
Minić, Dragica M.
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
A new Ni(II) complex, [Ni(L)(H2O)] (1), with diethyl 3,3'-(2,2'-(1,1'-(pyridine-2,6-diyl) bis(ethan-1-yl-1-ylidene)) bis(hydrazin-1-yl-2-ylidene)) bis(3-oxopropanoate) ligand (H2L) was synthesized as a potential chemotherapeutic agent. Polidentate ligand was coordinated to Ni(II) NNN-tridentately, in dianionic form, while monodentate water coordination completed square-planar geometry around metal. Structure in the solution was determined by NMR spectroscopy and the same coordination mode was observed in the solid state using IR spectroscopy and further verified by DFT calculations and electrochemical studies. Thermal stability of 1 was determined in both air and nitrogen atmosphere. Anticancer activity of 1 was investigated on acute monocytic leukemia (THP-1) and pancreatic adenocarcinoma (AsPC-1) cell lines. On THP-1 cells 1 induced powerful apoptotic response (ED50 = 10 +/- 3 mu M), which was revealed to be only partially caspase-dependent, with activation of caspase-8 as the domina...nt course. This suggested that experimentally validated covalent binding of 1 to DNA is not the only mechanism responsible for programmed cell death. This was supported with experiments on AsPC-1 cells. Although treatment of those cells with 1 resulted in poor apoptotic response, cell cycle changes showed concentration-dependent shifts indicating a dual mechanism of activity. This study also reviews the results of preliminary biological screening, which demonstrates that 1 displays a unique pattern of anticancer activity with at least two mechanisms involved.
Извор:
RSC Advances, 2016, 6, 110, 108726-108740Издавач:
- The Royal Society of Chemistry
Финансирање / пројекти:
- Интеракције природних производа, њихових деривата и комплексних једињења са протеинима и нуклеинским киселинама (RS-MESTD-Basic Research (BR or ON)-172055)
- Усмерена синтеза, структура и својства мултифункционалних материјала (RS-MESTD-Basic Research (BR or ON)-172057)
DOI: 10.1039/c6ra24604d
ISSN: 2046-2069
WoS: 000389342800068
Scopus: 2-s2.0-84997501324
Институција/група
Institut za opštu i fizičku hemijuTY - JOUR AU - Filipović, Nenad R. AU - Bjelogrlić, Snežana AU - Todorović, Tamara R. AU - Blagojević, Vladimir A. AU - Muller, Christian D. AU - Marinković, Aleksandar AU - Vujcić, Miroslava AU - Janović, Barbara AU - Malesević, Aleksandar AU - Begović, Nebojša AU - Sencanski, Milan AU - Minić, Dragica M. PY - 2016 UR - https://riofh.iofh.bg.ac.rs/handle/123456789/462 AB - A new Ni(II) complex, [Ni(L)(H2O)] (1), with diethyl 3,3'-(2,2'-(1,1'-(pyridine-2,6-diyl) bis(ethan-1-yl-1-ylidene)) bis(hydrazin-1-yl-2-ylidene)) bis(3-oxopropanoate) ligand (H2L) was synthesized as a potential chemotherapeutic agent. Polidentate ligand was coordinated to Ni(II) NNN-tridentately, in dianionic form, while monodentate water coordination completed square-planar geometry around metal. Structure in the solution was determined by NMR spectroscopy and the same coordination mode was observed in the solid state using IR spectroscopy and further verified by DFT calculations and electrochemical studies. Thermal stability of 1 was determined in both air and nitrogen atmosphere. Anticancer activity of 1 was investigated on acute monocytic leukemia (THP-1) and pancreatic adenocarcinoma (AsPC-1) cell lines. On THP-1 cells 1 induced powerful apoptotic response (ED50 = 10 +/- 3 mu M), which was revealed to be only partially caspase-dependent, with activation of caspase-8 as the dominant course. This suggested that experimentally validated covalent binding of 1 to DNA is not the only mechanism responsible for programmed cell death. This was supported with experiments on AsPC-1 cells. Although treatment of those cells with 1 resulted in poor apoptotic response, cell cycle changes showed concentration-dependent shifts indicating a dual mechanism of activity. This study also reviews the results of preliminary biological screening, which demonstrates that 1 displays a unique pattern of anticancer activity with at least two mechanisms involved. PB - The Royal Society of Chemistry T2 - RSC Advances T1 - Ni(II) complex with bishydrazone ligand: synthesis, characterization, DNA binding studies and pro-apoptotic and pro-differentiation induction in human cancerous cell lines EP - 108740 IS - 110 SP - 108726 VL - 6 DO - 10.1039/c6ra24604d UR - conv_636 ER -
@article{ author = "Filipović, Nenad R. and Bjelogrlić, Snežana and Todorović, Tamara R. and Blagojević, Vladimir A. and Muller, Christian D. and Marinković, Aleksandar and Vujcić, Miroslava and Janović, Barbara and Malesević, Aleksandar and Begović, Nebojša and Sencanski, Milan and Minić, Dragica M.", year = "2016", abstract = "A new Ni(II) complex, [Ni(L)(H2O)] (1), with diethyl 3,3'-(2,2'-(1,1'-(pyridine-2,6-diyl) bis(ethan-1-yl-1-ylidene)) bis(hydrazin-1-yl-2-ylidene)) bis(3-oxopropanoate) ligand (H2L) was synthesized as a potential chemotherapeutic agent. Polidentate ligand was coordinated to Ni(II) NNN-tridentately, in dianionic form, while monodentate water coordination completed square-planar geometry around metal. Structure in the solution was determined by NMR spectroscopy and the same coordination mode was observed in the solid state using IR spectroscopy and further verified by DFT calculations and electrochemical studies. Thermal stability of 1 was determined in both air and nitrogen atmosphere. Anticancer activity of 1 was investigated on acute monocytic leukemia (THP-1) and pancreatic adenocarcinoma (AsPC-1) cell lines. On THP-1 cells 1 induced powerful apoptotic response (ED50 = 10 +/- 3 mu M), which was revealed to be only partially caspase-dependent, with activation of caspase-8 as the dominant course. This suggested that experimentally validated covalent binding of 1 to DNA is not the only mechanism responsible for programmed cell death. This was supported with experiments on AsPC-1 cells. Although treatment of those cells with 1 resulted in poor apoptotic response, cell cycle changes showed concentration-dependent shifts indicating a dual mechanism of activity. This study also reviews the results of preliminary biological screening, which demonstrates that 1 displays a unique pattern of anticancer activity with at least two mechanisms involved.", publisher = "The Royal Society of Chemistry", journal = "RSC Advances", title = "Ni(II) complex with bishydrazone ligand: synthesis, characterization, DNA binding studies and pro-apoptotic and pro-differentiation induction in human cancerous cell lines", pages = "108740-108726", number = "110", volume = "6", doi = "10.1039/c6ra24604d", url = "conv_636" }
Filipović, N. R., Bjelogrlić, S., Todorović, T. R., Blagojević, V. A., Muller, C. D., Marinković, A., Vujcić, M., Janović, B., Malesević, A., Begović, N., Sencanski, M.,& Minić, D. M.. (2016). Ni(II) complex with bishydrazone ligand: synthesis, characterization, DNA binding studies and pro-apoptotic and pro-differentiation induction in human cancerous cell lines. in RSC Advances The Royal Society of Chemistry., 6(110), 108726-108740. https://doi.org/10.1039/c6ra24604d conv_636
Filipović NR, Bjelogrlić S, Todorović TR, Blagojević VA, Muller CD, Marinković A, Vujcić M, Janović B, Malesević A, Begović N, Sencanski M, Minić DM. Ni(II) complex with bishydrazone ligand: synthesis, characterization, DNA binding studies and pro-apoptotic and pro-differentiation induction in human cancerous cell lines. in RSC Advances. 2016;6(110):108726-108740. doi:10.1039/c6ra24604d conv_636 .
Filipović, Nenad R., Bjelogrlić, Snežana, Todorović, Tamara R., Blagojević, Vladimir A., Muller, Christian D., Marinković, Aleksandar, Vujcić, Miroslava, Janović, Barbara, Malesević, Aleksandar, Begović, Nebojša, Sencanski, Milan, Minić, Dragica M., "Ni(II) complex with bishydrazone ligand: synthesis, characterization, DNA binding studies and pro-apoptotic and pro-differentiation induction in human cancerous cell lines" in RSC Advances, 6, no. 110 (2016):108726-108740, https://doi.org/10.1039/c6ra24604d ., conv_636 .