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

• Published in: Journal of biological inorganic chemistry Vol. 20; no. 8; pp. 1287 - 1298
• Main Authors: Weintraub, Sagiv, Moskovitz, Yoni, Fleker, Ohad, Levy, Ariel R., Meir, Aviv, Ruthstein, Sharon, Benisvy, Laurent, Gruzman, Arie
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.12.2015
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - metabolism; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Biochemistry; Biological Mimicry; Biomedical and Life Sciences; Cell Line, Tumor; Coordination Complexes - chemistry; Coordination Complexes - metabolism; Coordination Complexes - pharmacology; Copper - chemistry; Drug Stability; Electrophoresis, Agar Gel; Humans; Iron - chemistry; Life Sciences; Mice; Microbiology; Molecular Structure; Original Paper; Rats; Superoxide Dismutase - chemistry; Superoxide Dismutase - metabolism; Water - chemistry; Anticancer drugs; Cytotoxicity; SOD mimetic; Tetra nuclear copper (II) complex; Apoptosis
• ISSN: 0949-8257; 1432-1327
• DOI: 10.1007/s00775-015-1307-x

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 Cu 4 (2,4-di- tert -butyl-6-(1H-imidazo- [1, 10] phenanthrolin-2-yl)phenol) 4 ]·10 CH 3 CN ( 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.