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Issue 110, 2016, Issue in Progress
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Ni(II) complex with bishydrazone ligand: synthesis, characterization, DNA binding studies and pro-apoptotic and pro-differentiation induction in human cancerous cell lines

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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.

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

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Publication details

The article was received on 02 Oct 2016, accepted on 04 Nov 2016 and first published on 07 Nov 2016


Article type: Paper
DOI: 10.1039/C6RA24604D
Citation: RSC Adv., 2016,6, 108726-108740
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    Ni(II) complex with bishydrazone ligand: synthesis, characterization, DNA binding studies and pro-apoptotic and pro-differentiation induction in human cancerous cell lines

    N. R. Filipović, S. Bjelogrlić, T. R. Todorović, V. A. Blagojević, C. D. Muller, A. Marinković, M. Vujčić, B. Janović, A. S. Malešević, N. Begović, M. Senćanski and D. M. Minić, RSC Adv., 2016, 6, 108726
    DOI: 10.1039/C6RA24604D

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