Ni(II) complex with bishydrazone ligand: synthesis, characterization, DNA binding studies and pro-apoptotic and pro-differentiation induction in human cancerous cell lines

2016
Authors
Filipović, Nenad R.
Bjelogrlić, Snežana K.

Todorović, Tamara

Blagojević, Vladimir A.

Muller, Christian D.

Marinković, Aleksandar

Vujčić, Miroslava T.

Janović, Barbara S.

Malešević, Aleksandar

Begović, Nebojša
Senćanski, Milan V.

Minić, Dragica M.

Article (Published version)
Metadata
Show full item recordAbstract
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.
Source:
RSC Advances, 2016, 6, 110, 108726-108740Publisher:
- Royal Soc Chemistry, Cambridge
Funding / projects:
- Interactions of natural products, their derivatives and coordination compounds with proteins and nucleic acids (RS-172055)
- Directed synthesis, structure and properties of multifunctional materials (RS-172057)
DOI: 10.1039/c6ra24604d
ISSN: 2046-2069
WoS: 000389342800068
Scopus: 2-s2.0-84997501324
Institution/Community
Tehnološko-metalurški fakultetTY - JOUR AU - Filipović, Nenad R. AU - Bjelogrlić, Snežana K. AU - Todorović, Tamara AU - Blagojević, Vladimir A. AU - Muller, Christian D. AU - Marinković, Aleksandar AU - Vujčić, Miroslava T. AU - Janović, Barbara S. AU - Malešević, Aleksandar AU - Begović, Nebojša AU - Senćanski, Milan V. AU - Minić, Dragica M. PY - 2016 UR - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/3315 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 EP - 108740 IS - 110 SP - 108726 VL - 6 DO - 10.1039/c6ra24604d ER -
@article{ author = "Filipović, Nenad R. and Bjelogrlić, Snežana K. and Todorović, Tamara and Blagojević, Vladimir A. and Muller, Christian D. and Marinković, Aleksandar and Vujčić, Miroslava T. and Janović, Barbara S. and Malešević, Aleksandar 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.", 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", pages = "108740-108726", number = "110", volume = "6", doi = "10.1039/c6ra24604d" }
Filipović, N. R., Bjelogrlić, S. K., Todorović, T., Blagojević, V. A., Muller, C. D., Marinković, A., Vujčić, M. T., Janović, B. S., Malešević, A., 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 Royal Soc Chemistry, Cambridge., 6(110), 108726-108740. https://doi.org/10.1039/c6ra24604d
Filipović NR, Bjelogrlić SK, Todorović T, Blagojević VA, Muller CD, Marinković A, Vujčić MT, Janović BS, Malešević A, 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 K., Todorović, Tamara, Blagojević, Vladimir A., Muller, Christian D., Marinković, Aleksandar, Vujčić, Miroslava T., Janović, Barbara S., Malešević, Aleksandar, 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 . .