caa a22 4500 605507546 CHVBK 20210128100632.0 cr unu---uuuuu 210128e20151201xx s 000 0 eng 10.1007/s00775-015-1307-x doi (NATIONALLICENCE)springer-10.1007/s00775-015-1307-x SOD mimetic activity and antiproliferative properties of a novel tetra nuclear copper (II) complex [Elektronische Daten] [Sagiv Weintraub, Yoni Moskovitz, Ohad Fleker, Ariel Levy, Aviv Meir, Sharon Ruthstein, Laurent Benisvy, Arie Gruzman] 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 96h 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. SBIC, 2015 Tetra nuclear copper (II) complex nationallicence Apoptosis nationallicence SOD mimetic nationallicence Cytotoxicity nationallicence Anticancer drugs nationallicence Weintraub Sagiv Department of Chemistry, Bar-Ilan University, 5290002, Ramat Gan, Israel aut Moskovitz Yoni Department of Chemistry, Bar-Ilan University, 5290002, Ramat Gan, Israel aut Fleker Ohad Department of Chemistry, Bar-Ilan University, 5290002, Ramat Gan, Israel aut Levy Ariel Department of Chemistry, Bar-Ilan University, 5290002, Ramat Gan, Israel aut Meir Aviv Department of Chemistry, Bar-Ilan University, 5290002, Ramat Gan, Israel aut Ruthstein Sharon Department of Chemistry, Bar-Ilan University, 5290002, Ramat Gan, Israel aut Benisvy Laurent Department of Chemistry, Bar-Ilan University, 5290002, Ramat Gan, Israel aut Gruzman Arie Department of Chemistry, Bar-Ilan University, 5290002, Ramat Gan, Israel aut JBIC Journal of Biological Inorganic Chemistry Springer Berlin Heidelberg 20/8(2015-12-01), 1287-1298 0949-8257 20:8<1287 2015 20 775 https://doi.org/10.1007/s00775-015-1307-x text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00775-015-1307-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Weintraub Sagiv Department of Chemistry, Bar-Ilan University, 5290002, Ramat Gan, Israel aut NATIONALLICENCE 700 1- Moskovitz Yoni Department of Chemistry, Bar-Ilan University, 5290002, Ramat Gan, Israel aut NATIONALLICENCE 700 1- Fleker Ohad Department of Chemistry, Bar-Ilan University, 5290002, Ramat Gan, Israel aut NATIONALLICENCE 700 1- Levy Ariel Department of Chemistry, Bar-Ilan University, 5290002, Ramat Gan, Israel aut NATIONALLICENCE 700 1- Meir Aviv Department of Chemistry, Bar-Ilan University, 5290002, Ramat Gan, Israel aut NATIONALLICENCE 700 1- Ruthstein Sharon Department of Chemistry, Bar-Ilan University, 5290002, Ramat Gan, Israel aut NATIONALLICENCE 700 1- Benisvy Laurent Department of Chemistry, Bar-Ilan University, 5290002, Ramat Gan, Israel aut NATIONALLICENCE 700 1- Gruzman Arie Department of Chemistry, Bar-Ilan University, 5290002, Ramat Gan, Israel aut NATIONALLICENCE 773 0- JBIC Journal of Biological Inorganic Chemistry Springer Berlin Heidelberg 20/8(2015-12-01), 1287-1298 0949-8257 20:8<1287 2015 20 775