Artificial nuclease and anticancer activity of a mononuclear copper(I) complex and a related binuclear double-stranded helicate

Levín, Pedro; Balsa, Lucía M.; León, Ignacio E.; Lemus, luis

Keywords: Nuclease, Helicate, Anticancer


Artificial nucleases have potential applications in the field of biotechnology and medicine. In particular, coordination compounds with nuclease activity are candidates as chemotherapeutic agents in the treatment of cancer. Here, we report the synthesis and characterization of a new mononuclear copper (I) complex derived of phenanthroline, [Cu(L1)2](ClO4), (1), and a related binuclear doublestranded helicate, [Cu2(L2)2](ClO4)2, (2). The structure of both complexes was confirmed in solid and solution phase through NMR, UV-Vis, elemental analysis, electrochemistry and X-ray diffraction. Interestingly, both complexes can operate as artificial nucleases against pBR322 plasmid DNA, with no addition of any oxidant agent such as hydrogen peroxide. The results of DNA cleavage show that the binuclear helicate has a higher activity, with a moderate activity at 1 µM (~30% DNA cleavage), while complete conversion from the supercoiled form to nicked and lineal form at 5 µM. The mononuclear complex shows only moderated activity at 25 µM (~44% DNA cleavage). Mechanistic studies by electrophoresis technique using ROS scavengers, showed that HO• radical and H2O2 are involved in the damage of DNA by oxidative process. Differences in the activity of the mono and bimetallic complexes are discussed in terms of the nuclearity, cationic charge, size and geometrical distortions from the copper atoms. Both copper(I) complexes were studied as cytotoxic agents in human bone (MG-63), breast (MCF-7) and colon (HT-29) cancer cell lines, presenting activity at the sub-micromolar concentration level. Results are in agreement with an oxidative mechanism induced by the copper(I) complexes through intracellular ROS generation.

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Fecha de publicación: 2019
Año de Inicio/Término: 11-16 Agosto 2019