Ni(II) complex with bishydrazone ligand: synthesis, characterization, DNA binding studies and pro-apoptotic and pro-differentiation induction in human cancerous cell lines
2016
Аутори
Filipovic, Nenad R.Bjelogrlić, Snežana K.
Todorović, Tamara
Blagojević, Vladimir A.
Muller, Christian D.
Marinković, Aleksandar D.
Vujčić, Miroslava
Janović, Barbara
Malešević, Aleksandar S.
Begovic, Nebojsa
Senćanski, 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:
- Royal Soc Chemistry, Cambridge
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
IHTMTY - JOUR AU - Filipovic, Nenad R. AU - Bjelogrlić, Snežana K. AU - Todorović, Tamara AU - Blagojević, Vladimir A. AU - Muller, Christian D. AU - Marinković, Aleksandar D. AU - Vujčić, Miroslava AU - Janović, Barbara AU - Malešević, Aleksandar S. AU - Begovic, Nebojsa AU - Senćanski, Milan AU - Minić, Dragica M. PY - 2016 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/2010 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 - Royal Soc Chemistry, Cambridge 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 = "Filipovic, Nenad R. and Bjelogrlić, Snežana K. and Todorović, Tamara and Blagojević, Vladimir A. and Muller, Christian D. and Marinković, Aleksandar D. and Vujčić, Miroslava and Janović, Barbara and Malešević, Aleksandar S. and Begovic, Nebojsa 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 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 = "Royal Soc Chemistry, Cambridge", 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" }
Filipovic, N. R., Bjelogrlić, S. K., Todorović, T., Blagojević, V. A., Muller, C. D., Marinković, A. D., Vujčić, M., Janović, B., Malešević, A. S., Begovic, 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 Soc Chemistry, Cambridge., 6(110), 108726-108740. https://doi.org/10.1039/c6ra24604d
Filipovic NR, Bjelogrlić SK, Todorović T, Blagojević VA, Muller CD, Marinković AD, Vujčić M, Janović B, Malešević AS, Begovic N, 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(110):108726-108740. doi:10.1039/c6ra24604d .
Filipovic, Nenad R., Bjelogrlić, Snežana K., Todorović, Tamara, Blagojević, Vladimir A., Muller, Christian D., Marinković, Aleksandar D., Vujčić, Miroslava, Janović, Barbara, Malešević, Aleksandar S., Begovic, Nebojsa, 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, no. 110 (2016):108726-108740, https://doi.org/10.1039/c6ra24604d . .