Mixed ligand complexes of Co(II), Ni(II) and Cu(II) with quercetin and diimine ligands: synthesis, characterization, anti-cancer and anti-oxidant activity


MUTLU GENÇKAL H., Erkisa M., Alper P., ŞAHİN S., Ulukaya E., ARI F.

JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY, vol.25, no.1, pp.161-177, 2020 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 25 Issue: 1
  • Publication Date: 2020
  • Doi Number: 10.1007/s00775-019-01749-z
  • Title of Journal : JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
  • Page Numbers: pp.161-177

Abstract

In this work, mixed ligand complexes of Co(II) Ni(II) and Cu(II) were synthesized using quercetin and diimine (1,10-phenanthroline or 2,2 '-bipyiridine) ligands. The obtained Ni(II) and Co(II) complexes are new and the Cu(II) complexes are synthesized by different method from the literature. The characterization of complexes was performed by elemental analysis, thermogravimetric analysis, ESI-MS, UV-visible and infrared spectral analyses, magnetic susceptibility and molar conductivity measurements. It was found that quercetin, diimine and metal(II) ion form 1:1:1 complexes. Resulting data supported octahedral geometry for Ni(II) and Co(II) complexes and square pyramidal geometry for Cu(II) complexes. The proposed compositions are [Co(queH-1)Cl(phen)(H2O)]center dot 2H(2)O (1, queH = quercetin, phen = 1,10-phenanthroline), [Ni(queH-1)Cl(phen)(H2O)]center dot 2H(2)O (2), [Cu(queH-1)Cl(phen)]center dot 2.5H(2)O (3) and [Cu(queH-1)Cl(bpy)]center dot 2H(2)O (4, bpy = 2,2 '-bipyiridine). Antioxidant capacity and total phenolic content of complexes measured by Folin-Ciocalteu and ABTS methods. Anti-cancer effect of these compounds were tested against different cancer cells (A549, PC-3, HeLa and MCF-7). Apoptosis identified by the fluorescence imaging, caspase cleaved cytokeratin-18 and flow cytometry analysis (annexin V, caspase 3/7, mitochondria membrane potential and oxidative stress). As a result, Cu(II) complexes are more effective than the other compounds and Complex 3 is a promising anti-cancer compound against breast cancer MCF-7 and MDA-MB-231 cells (IC50 values are 2.4 and 5.4 mu M for 48 h, respectively). Flow cytometry analysis exhibited that Complex 3 caused apoptosis in MCF-7 cells. These results support that Complex 3 has anticancer activity and can be a potential anticancer agent especially in breast cancer.