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Synthesis, characterization and biological activity of copper(II) complexes with ligands derived from β-amino acids

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Abstract

Two copper(II) complexes with ligands derived from β-amino acids, 2-(1-aminocyclohexyl)acetic acid L1 and 2-(1-amino-4-(tert-butyl)cyclohexyl)acetic acid L2, were synthesized and characterized by microanalysis, infrared, UV–Vis and EPR spectra. The spectroscopically predicted structure of the square-planar copper(II) complex with 2-(1-aminocyclohexyl)-acetic acid C1 was confirmed by single-crystal X-ray analysis. The biological activities (antitumor activities and interaction with DNA) of the compounds were also investigated. The interactions of both complexes with calf thymus (CT) and herring testes (HT) DNA were examined by stopped-flow spectroscopy, by absorption (UV–Vis) and by emission spectral studies (ethidium bromide displacement studies). Both complexes were found to react a bit faster with HT-DNA than with CT-DNA. The obtained binding constants suggested a moderate intercalative binding mode between the complexes and DNA. In addition, fluorescence spectrometry of bovine serum albumin with the complexes showed a good fluorescence quenching of the complexes. The obtained copper(II) complexes have a relatively low cytotoxic effect on murine mammary carcinoma cell line, 4T1, a moderate effect on murine colon carcinoma cell line, CT26, and a relatively high cytotoxicity toward murine lung cancer cells, LLC1.

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Acknowledgements

The authors are grateful to the Ministry of Science and Technological Development of the Republic of Serbia for financial support (Grants Nos. 172016, 172034, 175069, 175103, 172011) and Faculty of Medical Sciences for grant MP 2014/02. This work was also supported by the project VEGA 1/0598/14. We thank prof. Ana Popović-Bijelić and prof. Miloš Mojović (EPR Lab, Faculty of Physical Chemistry, University of Belgrade) for acquiring and analyzing the EPR spectra.

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Authors and Affiliations

  1. Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovića 69, Kragujevac, 34000, Republic of Serbia

    Andriana M. Bukonjić, Dušan Lj. Tomović, Ana S. Stanković & Gordana P. Radić

  2. Department of Chemistry, Faculty of Science, University of Kragujevac, Radoja Domanovića 12, Kragujevac, 34000, Republic of Serbia

    Verica V. Jevtić, Zoran R. Ratković, Jovana V. Bogojeski & Srećko R. Trifunović

  3. Department of Microbiology and Immunology, Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovića 69, Kragujevac, 34000, Republic of Serbia

    Jelena Z. Milovanović, Dragana B. Đorđević, Aleksandar N. Arsenijević & Marija Z. Milovanović

  4. Institute of Chemistry, P.J. Safárik University, Moyzesova 11, 041 54, Kosice, Slovakia

    Ivan Potočňák

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  1. Andriana M. Bukonjić
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Correspondence to Jovana V. Bogojeski or Gordana P. Radić.

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Bukonjić, A.M., Tomović, D.L., Stanković, A.S. et al. Synthesis, characterization and biological activity of copper(II) complexes with ligands derived from β-amino acids. Transit Met Chem 44, 65–76 (2019). https://doi.org/10.1007/s11243-018-0270-0

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