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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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2016
10.1039-C6RA24604D.pdf (1.577Mb)
Authors
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.
Article (Accepted Version)
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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 cour...se. 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).

Keywords:
Ni(II) complexes / bishydrazone / DNA binding / anticancer activity
Source:
RSC Advances, 2016, 110, 108726-108740
Projects:
  • Directed synthesis, structure and properties of multifunctional materials (RS-172057)
  • COST Action CM1106 StemChem – “Chemical Approaches to Targeting Drug Resistance in Cancer Stem Cells”

DOI: 10.1039/C6RA24604D

ISSN: 2046-2069

WoS: 000389342800068

Scopus: 2-s2.0-84997501324
[ Google Scholar ]
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URI
http://dais.sanu.ac.rs/123456789/860
Collections
  • ITN SANU - Opšta kolekcija / ITS SASA - General collection
Institution
Институт техничких наука САНУ / Institute of Technical Sciences SASA

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