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.
authors.affiliation: Department of Chemistry, Bar-Ilan University, 5290002, Ramat Gan, Israel.
authors.forename: Sagiv
authors.initials: S
authors.lastname: Weintraub
authors.affiliation: Department of Chemistry, Bar-Ilan University, 5290002, Ramat Gan, Israel.
authors.forename: Yoni
authors.initials: Y
authors.lastname: Moskovitz
authors.affiliation: Department of Chemistry, Bar-Ilan University, 5290002, Ramat Gan, Israel.
authors.forename: Ohad
authors.initials: O
authors.lastname: Fleker
authors.affiliation: Department of Chemistry, Bar-Ilan University, 5290002, Ramat Gan, Israel.
authors.forename: Ariel R
authors.initials: AR
authors.lastname: Levy
authors.affiliation: Department of Chemistry, Bar-Ilan University, 5290002, Ramat Gan, Israel.
authors.forename: Aviv
authors.initials: A
authors.lastname: Meir
authors.affiliation: Department of Chemistry, Bar-Ilan University, 5290002, Ramat Gan, Israel.
authors.forename: Sharon
authors.initials: S
authors.lastname: Ruthstein
authors.affiliation: Department of Chemistry, Bar-Ilan University, 5290002, Ramat Gan, Israel. benisvy@gmail.com.
authors.forename: Laurent
authors.initials: L
authors.lastname: Benisvy
authors.affiliation: Department of Chemistry, Bar-Ilan University, 5290002, Ramat Gan, Israel. gruzmaa@biu.ac.il.
authors.forename: Arie
authors.initials: A
authors.lastname: Gruzman
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D000067558:Biological Mimicry; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D003300:Copper / Q000737:chemistry*; D004355:Drug Stability; D004587:Electrophoresis, Agar Gel; D006801:Humans; D007501:Iron / Q000737:chemistry; D051379:Mice; D015394:Molecular Structure; D051381:Rats; D013482:Superoxide Dismutase / Q000737:chemistry / Q000378:metabolism*; D014867:Water / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D014867:Water; D003300:Copper; D007501:Iron; D013482:Superoxide Dismutase
keywords: Anticancer drugs; Apoptosis; Cytotoxicity; SOD mimetic; Tetra nuclear copper (II) complex