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SOD mimetic activity and antiproliferative properties of a novel tetra nuclear copper (II) complex

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Abstract

The search for novel anticancer therapeutic agents is an urgent and important issue in medicinal chemistry. Here, we report on the biological activity of the copper-based bioinorganic complex Cu4 (2,4-di-tert-butyl-6-(1H-imidazo- [1, 10] phenanthrolin-2-yl)phenol)4]·10 CH3CN (2), which was tested in rat L6 myotubes, mouse NSC-34 motor neurone-like cells, and HepG-2 human liver carcinoma. Upon 96 h incubation, 2 exhibited a significant cytotoxic effect on all three types of cells via activation of two cell death mechanisms (apoptosis and necrosis). Complex 2 exhibited better potency and efficacy than the canonical cytotoxic drug cisplatin. Moreover, during shorter incubations, complex 2 demonstrated a significant SOD mimetic activity, and it was more effective and more potent than the well-known SOD mimetic TEMPOL. In addition, complex 2 was able to interact with DNA and, cleave DNA in the presence of sodium ascorbate. This study shows the potential of using polynuclear redox active compounds for developing novel anticancer drugs through SOD-mimetic redox pathways.

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Acknowledgments

This study was partly supported by Bar-Ilan University‘s new faculty Grants for AG and LB. We thank Dr. M. Kanovsky and S. Manch for editing the manuscript.

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Authors and Affiliations

  1. Department of Chemistry, Bar-Ilan University, 5290002, Ramat Gan, Israel

    Sagiv Weintraub, Yoni Moskovitz, Ohad Fleker, Ariel R. Levy, Aviv Meir, Sharon Ruthstein, Laurent Benisvy & Arie Gruzman

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  1. Sagiv Weintraub
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  2. Yoni Moskovitz
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  3. Ohad Fleker
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  4. Ariel R. Levy
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  5. Aviv Meir
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  6. Sharon Ruthstein
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  7. Laurent Benisvy
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  8. Arie Gruzman
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Corresponding authors

Correspondence to Laurent Benisvy or Arie Gruzman.

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775_2015_1307_MOESM1_ESM.pdf

Electronic Supplementary Material (ESM) is published in the electronic edition of this journal. It provides material about the cytotoxic effect of test compounds, the effect of complex 2 on xanthine oxidase, and the catalase activity of complex 2. (PDF 116 kb)

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Weintraub, S., Moskovitz, Y., Fleker, O. et al. SOD mimetic activity and antiproliferative properties of a novel tetra nuclear copper (II) complex. J Biol Inorg Chem 20, 1287–1298 (2015). https://doi.org/10.1007/s00775-015-1307-x

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  • DOI: https://doi.org/10.1007/s00775-015-1307-x

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