title: Copper(II) complexes with new fluoroquinolones: Synthesis, structure, spectroscopic and theoretical study, DNA damage, cytotoxicity and antiviral activity.
abstract: Copper(II) complexes with fluoroquinolones in the presence of the nitrogen donor heterocyclic ligands 1,10-phenanthroline have been considered in detail. The phenanthroline moiety was introduced into the ligand environment with the aim to determine whether the nuclease activity is feasible. All suitable X-ray structures of the complexes under study reveal a distorted square pyramidal coordination geometry for Cu(II) atom. The conformational and spectroscopic (FT-IR and UV-visible) behavior has been analyzed and has been interpreted with respect to B3LYP/6-311G* calculations including molecular dynamics. The ability of the complexes to cleave DNA was studied by agarose gel electrophoresis with plasmid DNA pBSK+. The results have confirmed that the complexes under study behave as the chemical nucleases. Nuclease like activity in the absence of hydrogen peroxide allows us to deduce an interaction of the complexes with the DNA resulting in the conversion of supercoiled circular DNA to the nicked form. The DNA cleavage activity enhanced by the presence of hydrogen peroxide demonstrates the participation of reactive oxygen species, such as superoxide radical anions and hydroxyl radicals which presence was confirmed independently using the standard radical scavenging agents. It has been suggested that the radical formation through the Fenton/Haber-Weiss reaction is mediated by the redox cycling mechanisms with the participation of cupric/cuprous ions. Cytotoxic activity was evaluated as the 50% cytotoxic concentration (CC50). The potential effects of tested compounds on replication of murine gammaherpesvirus 68 (MHV-68) under in vitro conditions were also evaluated. However, no antiviral activity against MHV-68 was observed.
authors.affiliation: Institute of Physical Chemistry and Chemical Physics, Faculty of Chemical and Food Technology, Slovak University of Technology in Bratislava, Radlinského 9, SK-812 37 Bratislava, Slovak Republic. Electronic address: sandra.dorotikova@stuba.sk.
authors.forename: Sandra
authors.initials: S
authors.lastname: Dorotíková
authors.affiliation: Institute of Physical Chemistry and Chemical Physics, Faculty of Chemical and Food Technology, Slovak University of Technology in Bratislava, Radlinského 9, SK-812 37 Bratislava, Slovak Republic.
authors.forename: Júlia
authors.initials: J
authors.lastname: Kožíšková
authors.affiliation: Institute of Physical Chemistry and Chemical Physics, Faculty of Chemical and Food Technology, Slovak University of Technology in Bratislava, Radlinského 9, SK-812 37 Bratislava, Slovak Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Malček
authors.affiliation: Department of Chemistry, Constantine the Philosopher University in Nitra, Faculty of Natural Sciences, Tr. A. Hlinku 1, SK-949 74 Nitra, Slovak Republic.
authors.forename: Klaudia
authors.initials: K
authors.lastname: Jomová
authors.affiliation: Institute of Physical Chemistry and Chemical Physics, Faculty of Chemical and Food Technology, Slovak University of Technology in Bratislava, Radlinského 9, SK-812 37 Bratislava, Slovak Republic; Department of Chemical Theory of Drugs, Faculty of Pharmacy, Comenius University in Bratislava, Kalinčiakova 8, SK-832 32 Bratislava, Slovak Republic.
authors.forename: Peter
authors.initials: P
authors.lastname: Herich
authors.affiliation: Institute of Organic Chemistry, Catalysis and Petrochemistry, Faculty of Chemical and Food Technology, Slovak University of Technology in Bratislava, Radlinského 9, SK-812 37 Bratislava, Slovak Republic.
authors.forename: Kristína
authors.initials: K
authors.lastname: Plevová
authors.affiliation: Department of Microbiology and Virology, Faculty of Natural Sciences, Comenius University in Bratislava, Mlynská dolina, SK-842 15 Bratislava, Slovak Republic.
authors.forename: Katarína
authors.initials: K
authors.lastname: Briestenská
authors.affiliation: Department of Microbiology and Virology, Faculty of Natural Sciences, Comenius University in Bratislava, Mlynská dolina, SK-842 15 Bratislava, Slovak Republic.
authors.forename: Anna
authors.initials: A
authors.lastname: Chalupková
authors.affiliation: Department of Microbiology and Virology, Faculty of Natural Sciences, Comenius University in Bratislava, Mlynská dolina, SK-842 15 Bratislava, Slovak Republic; Institute of Virology, Slovak Academy of Sciences, Dúbravská cesta 9, SK-845 05 Bratislava, Slovak Republic.
authors.forename: Jela
authors.initials: J
authors.lastname: Mistríková
authors.affiliation: Institute of Organic Chemistry, Catalysis and Petrochemistry, Faculty of Chemical and Food Technology, Slovak University of Technology in Bratislava, Radlinského 9, SK-812 37 Bratislava, Slovak Republic.
authors.forename: Viktor
authors.initials: V
authors.lastname: Milata
authors.affiliation: Institute of Physical Chemistry and Chemical Physics, Faculty of Chemical and Food Technology, Slovak University of Technology in Bratislava, Radlinského 9, SK-812 37 Bratislava, Slovak Republic.
authors.forename: Dana
authors.initials: D
authors.lastname: Dvoranová
authors.affiliation: Institute of Physical Chemistry and Chemical Physics, Faculty of Chemical and Food Technology, Slovak University of Technology in Bratislava, Radlinského 9, SK-812 37 Bratislava, Slovak Republic.
authors.forename: Lukáš
authors.initials: L
authors.lastname: Bučinský
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002522:Chlorocebus aethiops; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D053837:DNA Cleavage / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects*; D024841:Fluoroquinolones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D051379:Mice; D008956:Models, Chemical; D008968:Molecular Conformation; D018144:Rhadinovirus / Q000187:drug effects; D013055:Spectrophotometry, Infrared; D014709:Vero Cells
chemical_list: D000998:Antiviral Agents; D056831:Coordination Complexes; D024841:Fluoroquinolones; D003300:Copper
keywords: Antiviral activity; Copper(II) complex; Crystal structure; DNA interaction; Fluoroquinolone; Molecular dynamics simulation