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

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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)]∙2H2O (1, queH = quercetin, phen = 1,10-phenanthroline), [Ni(queH-1)Cl(phen)(H2O)]∙2H2O (2), [Cu(queH-1)Cl(phen)]∙2.5H2O (3) and [Cu(queH-1)Cl(bpy)]∙2H2O (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 µM 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.

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Acknowledgements

We thank G. Done for their technical assistance and the Research Fund of Bursa Uludag University for the financial support given to the research project (Project Number OUAP (F)–2014/27).

Funding

This work was supported by grants from the Research Fund of Bursa Uludag University for the financial support given to the research Project (Project Number OUAP (F)–2014/27).

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  1. Merve Erkisa & Engin Ulukaya

    Present address: Department of Clinical Biochemistry, Faculty of Medicine, Istinye University, 34010, Istanbul, Turkey

  2. Pınar Alper

    Present address: Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, Istanbul University, 34093, Istanbul, Turkey

Authors and Affiliations

  1. Department of Chemistry, Faculty of Science and Arts, Bursa Uludag University, 16059, Bursa, Turkey

    Hasene Mutlu Gençkal & Saliha Sahin

  2. Department of Biology, Faculty of Science and Arts, Bursa Uludag University, 16059, Bursa, Turkey

    Merve Erkisa, Pınar Alper & Ferda Ari

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Contributions

FA, HMG, and EU contributed to the study design, FA, HMG, ME and PA performed experiments, FA and HMG, performed the analysis of the data, SS setup und performed phenolic contents and antioxidant capacities of complexes, FA and HMG, contributed to the writing of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Ferda Ari.

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Mutlu Gençkal, H., Erkisa, M., Alper, P. et al. Mixed ligand complexes of Co(II), Ni(II) and Cu(II) with quercetin and diimine ligands: synthesis, characterization, anti-cancer and anti-oxidant activity. J Biol Inorg Chem 25, 161–177 (2020). https://doi.org/10.1007/s00775-019-01749-z

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