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

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

doi:10.1007/s00775-015-1307-x

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

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

Bar-Ilan University

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

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.

Original language	English
Pages (from-to)	1287-1298
Number of pages	12
Journal	Journal of Biological Inorganic Chemistry
Volume	20
Issue number	8
DOIs	https://doi.org/10.1007/s00775-015-1307-x
State	Published - 1 Dec 2015

Bibliographical note

Publisher Copyright:
© 2015 SBIC.

Funding

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.

Funders	Funder number
Bar-Ilan University

Keywords

Anticancer drugs
Apoptosis
Cytotoxicity
SOD mimetic
Tetra nuclear copper (II) complex

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10.1007/s00775-015-1307-x

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

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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AU - Ruthstein, Sharon

AU - Benisvy, Laurent

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

Abstract

Bibliographical note

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Keywords

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