TY  - JOUR
AU  - Filipović, Nenad R.
AU  - Bjelogrlić, Snežana
AU  - Todorović, Tamara R.
AU  - Blagojević, Vladimir A.
AU  - Muller,  Christian D.
AU  - Marinković, Aleksandar
AU  - Vujčić, Miroslava
AU  - Janović, Barbara
AU  - Malešević, Aleksandar
AU  - Begović, Nebojša N.
AU  - Senćanski, Milan
AU  - Minić, Dragica M.
PY  - 2016
UR  - https://dais.sanu.ac.rs/123456789/2309
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 μM), 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  - 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
SP  - 108726
EP  - 108740
VL  - 6
DO  - 10.1039/C6RA24604D
UR  - https://hdl.handle.net/21.15107/rcub_dais_2309
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 Vujčić, Miroslava and Janović, Barbara and Malešević, Aleksandar and Begović, Nebojša N. and Senćanski, 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 μM), 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 = "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 = "108726-108740",
volume = "6",
doi = "10.1039/C6RA24604D",
url = "https://hdl.handle.net/21.15107/rcub_dais_2309"
}

Filipović, N. R., Bjelogrlić, S., Todorović, T. R., Blagojević, V. A., Muller, C. D., Marinković, A., Vujčić, M., Janović, B., Malešević, A., Begović, N. N., Senćanski, 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
Royal Society of Chemistry., 6, 108726-108740.
https://doi.org/10.1039/C6RA24604D
https://hdl.handle.net/21.15107/rcub_dais_2309

Filipović NR, Bjelogrlić S, Todorović TR, Blagojević VA, Muller CD, Marinković A, Vujčić M, Janović B, Malešević A, Begović NN, Senćanski 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;6:108726-108740.
doi:10.1039/C6RA24604D
https://hdl.handle.net/21.15107/rcub_dais_2309 .

Filipović, Nenad R., Bjelogrlić, Snežana, Todorović, Tamara R., Blagojević, Vladimir A., Muller,  Christian D., Marinković, Aleksandar, Vujčić, Miroslava, Janović, Barbara, Malešević, Aleksandar, Begović, Nebojša N., Senćanski, 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 (2016):108726-108740,
https://doi.org/10.1039/C6RA24604D .,
https://hdl.handle.net/21.15107/rcub_dais_2309 .

TY  - JOUR
AU  - Filipović, Nenad R.
AU  - Bjelogrlić, Snežana
AU  - Todorović, Tamara R.
AU  - Blagojević, Vladimir A.
AU  - Muller, Christian D.
AU  - Marinković, Aleksandar
AU  - Vujčić, Miroslava
AU  - Janović, Barbara
AU  - Malešević, Aleksandar
AU  - Begović, Nebojša N.
AU  - Senćanski, Milan
AU  - Minić, Dragica M.
PY  - 2016
UR  - https://dais.sanu.ac.rs/123456789/860
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 µM), 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.

The authors acknowledge networking support by the COST Action CM1106 StemChem – “Chemical Approaches to Targeting Drug Resistance in Cancer Stem Cells”. The work was funded by the Ministry of Education, Science and Technological Development of the Republic of Serbia (Grant 172055).
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
SP  - 108726
EP  - 108740
VL  - 110
VL  - 6
DO  - 10.1039/C6RA24604D
UR  - https://hdl.handle.net/21.15107/rcub_dais_860
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 Vujčić, Miroslava and Janović, Barbara and Malešević, Aleksandar and Begović, Nebojša N. and Senćanski, 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 µM), 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.

The authors acknowledge networking support by the COST Action CM1106 StemChem – “Chemical Approaches to Targeting Drug Resistance in Cancer Stem Cells”. The work was funded by the Ministry of Education, Science and Technological Development of the Republic of Serbia (Grant 172055).",
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 = "108726-108740",
volume = "110, 6",
doi = "10.1039/C6RA24604D",
url = "https://hdl.handle.net/21.15107/rcub_dais_860"
}

Filipović, N. R., Bjelogrlić, S., Todorović, T. R., Blagojević, V. A., Muller, C. D., Marinković, A., Vujčić, M., Janović, B., Malešević, A., Begović, N. N., Senćanski, 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, 110, 108726-108740.
https://doi.org/10.1039/C6RA24604D
https://hdl.handle.net/21.15107/rcub_dais_860

Filipović NR, Bjelogrlić S, Todorović TR, Blagojević VA, Muller CD, Marinković A, Vujčić M, Janović B, Malešević A, Begović NN, Senćanski 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;110:108726-108740.
doi:10.1039/C6RA24604D
https://hdl.handle.net/21.15107/rcub_dais_860 .

Filipović, Nenad R., Bjelogrlić, Snežana, Todorović, Tamara R., Blagojević, Vladimir A., Muller, Christian D., Marinković, Aleksandar, Vujčić, Miroslava, Janović, Barbara, Malešević, Aleksandar, Begović, Nebojša N., Senćanski, 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, 110 (2016):108726-108740,
https://doi.org/10.1039/C6RA24604D .,
https://hdl.handle.net/21.15107/rcub_dais_860 .