TY  - JOUR
AU  - Filipović, Nenad R.
AU  - Bjelogrlić, Snežana
AU  - Todorović, Tamara R.
AU  - Blagojević, Vladimir A.
AU  - Muller, Christian D.
AU  - Marinković, Aleksandar D.
AU  - Vujčić, Miroslava T.
AU  - Janović, Barbara S.
AU  - Malešević, Aleksandar S.
AU  - Begović, Nebojša
AU  - Senćanski, Milan V.
AU  - Minić, Dragica M.
PY  - 2016
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1331
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.
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
VL  - 6
IS  - 110
SP  - 108726
EP  - 108740
DO  - 10.1039/c6ra24604d
ER  - 

@article{
author = "Filipović, Nenad R. and Bjelogrlić, Snežana and Todorović, Tamara R. and Blagojević, Vladimir A. and Muller, Christian D. and Marinković, Aleksandar D. and Vujčić, Miroslava T. and Janović, Barbara S. and Malešević, Aleksandar S. and Begović, Nebojša and Senćanski, Milan V. 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.",
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",
volume = "6",
number = "110",
pages = "108726-108740",
doi = "10.1039/c6ra24604d"
}

Filipović, N. R., Bjelogrlić, S., Todorović, T. R., Blagojević, V. A., Muller, C. D., Marinković, A. D., Vujčić, M. T., Janović, B. S., Malešević, A. S., Begović, N., Senćanski, M. V.,& 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, 6(110), 108726-108740.
https://doi.org/10.1039/c6ra24604d

Filipović NR, Bjelogrlić S, Todorović TR, Blagojević VA, Muller CD, Marinković AD, Vujčić MT, Janović BS, Malešević AS, Begović N, Senćanski MV, 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 .

Filipović, Nenad R., Bjelogrlić, Snežana, Todorović, Tamara R., Blagojević, Vladimir A., Muller, Christian D., Marinković, Aleksandar D., Vujčić, Miroslava T., Janović, Barbara S., Malešević, Aleksandar S., Begović, Nebojša, Senćanski, Milan V., 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 . .