Synthesis, characterization, cytotoxicity and antiangiogenic activity of copper(II) complexes with 1-adamantoyl hydrazone bearing pyridine rings

Marko V Rodić; Vukadin M Leovac; Ljiljana S Jovanović; Vojislav Spasojević; Milan D Joksović; Tatjana Stanojković; Ivana Z Matić; Ljiljana S Vojinović-Ješić; Violeta Marković

doi:10.1016/j.ejmech.2016.03.003

Synthesis, characterization, cytotoxicity and antiangiogenic activity of copper(II) complexes with 1-adamantoyl hydrazone bearing pyridine rings

Eur J Med Chem. 2016 Jun 10:115:75-81. doi: 10.1016/j.ejmech.2016.03.003. Epub 2016 Mar 8.

Authors

Marko V Rodić¹, Vukadin M Leovac², Ljiljana S Jovanović¹, Vojislav Spasojević³, Milan D Joksović⁴, Tatjana Stanojković⁵, Ivana Z Matić⁵, Ljiljana S Vojinović-Ješić¹, Violeta Marković⁴

Affiliations

¹ University of Novi Sad, Faculty of Sciences, Trg D. Obradovića 3, 21000, Novi Sad, Serbia.
² University of Novi Sad, Faculty of Sciences, Trg D. Obradovića 3, 21000, Novi Sad, Serbia. Electronic address: vukadin.leovac@dh.uns.ac.rs.
³ University of Belgrade, Institute of Nuclear Sciences Vinča, Condensed Matter Physics Laboratory, P.O. Box 522, 11001, Belgrade, Serbia.
⁴ University of Kragujevac, Faculty of Science, Department of Chemistry, R. Domanovića 12, 34000, Kragujevac, Serbia.
⁵ Institute of Oncology and Radiology of Serbia, Pasterova 14, 11000, Belgrade, Serbia.

PMID: 27084495
DOI: 10.1016/j.ejmech.2016.03.003

Abstract

Three novel copper complexes with tridentate N2O ligand di(2-pyridil) ketone 1-adamantoyl hydrazone (Addpy) of the formula [Cu(II)2Cu(I)2(Addpy)2Br2(μ-Br4)] (1), catena-poly[CuCl(μ-Addpy)(μ-Cl)CuCl2]n (2) and [Cu(Addpy)(NCS)2] (3) were synthesized. Complexes are characterized by X-ray crystallography, spectral (UV-Vis, FTIR), electrochemical (CV) analyses, and magnetochemical measurements. Investigation of anticancer potential of Cu(II) complexes, mode of cell death, apoptosis, and inhibition of angiogenesis were performed. All tested malignant cell lines (HeLa, LS174, A549, K562, and MDA-MB-231) showed high sensitivity to the examined Cu(II) complexes. It has been shown that the complexes induce apoptosis in the caspase 3-dependent manner, whereas the anti-angiogenic effects of 1, 2, and 3 have been confirmed in EA.hy926 cells using a tube formation assay.

Keywords: Angiogenesis; Caspase-3; Copper(II) complexes; Hydrazones; Physico-chemical characterization.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adamantane / analogs & derivatives*
Adamantane / chemistry
Adamantane / pharmacology
Angiogenesis Inhibitors / chemical synthesis
Angiogenesis Inhibitors / chemistry
Angiogenesis Inhibitors / pharmacology*
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Cell Proliferation / drug effects
Cell Survival / drug effects
Copper / chemistry
Copper / pharmacology*
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Hydrazones / chemistry
Hydrazones / pharmacology*
Molecular Structure
Neovascularization, Pathologic / drug therapy*
Neovascularization, Pathologic / pathology
Organometallic Compounds / chemical synthesis
Organometallic Compounds / chemistry
Organometallic Compounds / pharmacology*
Pyridines / chemistry
Pyridines / pharmacology*
Structure-Activity Relationship
Tumor Cells, Cultured

Substances

1-adamantoyl hydrazone
Angiogenesis Inhibitors
Antineoplastic Agents
Hydrazones
Organometallic Compounds
Pyridines
Copper
pyridine
Adamantane