title: New silver complexes with bioactive glycine and nicotinamide molecules - Characterization, DNA binding, antimicrobial and anticancer evaluation.
abstract: This study introduces a pair of newly synthesized silver complexes, [Ag2(HGly)2]n(NO3)2n(1) and [Ag(Nam)2]NO3·H2O (2) (Gly - glycine, Nam - nicotinamide), that were prepared and characterized by relevant methods in solid state (elemental, spectral, thermal and structural analysis) and their stability in solution was verified by1H NMR measurements. Moreover, suitable reaction conditions were observed by potentiometry depending on pH in case of binary system Ag-Gly. X-ray analysis confirmed argentophilic interactions in complex 1 with an Ag1-Ag2 distance of 2.8018(6) Å. Antimicrobial testing indicates higher growth inhibition effect of complex 1 than complex 2. Moreover the effectivity of both complexes against bacteria (Staphylococcus aureus and Escherichia coli) is superior (or similar) to that of the commercially available Ag(I) sulfadiazine, AgSD (used, for example, in Dermazine cream). The binding of the Ag(I) complexes to calf thymus DNA was investigated using electronic absorption, fluorescence and circular dichroism spectrophotometry. The Stern-Volmer quenching constants obtained from the linear quenching plot were estimated in the range from 2.01×103to 20.34×103M-1. The results of topoisomerase I and topoisomerase II (Topo I and Topo II) inhibition assay suggested that complex 2 inhibits the enzyme activity of both enzymes at a concentration of 2μM. The cytotoxicity of both complexes on L1210 leukemia cells was revealed to be approximately three times higher than that of cisplatin. Moreover, the new Ag(I) complexes also induced apoptosis of the leukemia cells. The high DNA binding activity of these complexes is considered to be responsible for their cytotoxic effects.
authors.affiliation: Department of Inorganic Chemistry, Faculty of Science, P. J. Šafárik University, Moyzesova 11, SK-041 54 Košice, Slovak Republic.
authors.forename: Michaela
authors.initials: M
authors.lastname: Rendošová
authors.affiliation: Department of Inorganic Chemistry, Faculty of Science, P. J. Šafárik University, Moyzesova 11, SK-041 54 Košice, Slovak Republic. Electronic address: zuzana.vargova@upjs.sk.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Vargová
authors.affiliation: Department of Inorganic Chemistry, Faculty of Science, P. J. Šafárik University, Moyzesova 11, SK-041 54 Košice, Slovak Republic.
authors.forename: Juraj
authors.initials: J
authors.lastname: Kuchár
authors.affiliation: Department of Biochemistry, Faculty of Science, P. J. Šafárik University, Moyzesova 11, SK-041 54 Košice, Slovak Republic.
authors.forename: Danica
authors.initials: D
authors.lastname: Sabolová
authors.affiliation: Department of Biochemistry, Faculty of Science, P. J. Šafárik University, Moyzesova 11, SK-041 54 Košice, Slovak Republic.
authors.forename: Štefan
authors.initials: Š
authors.lastname: Levoča
authors.affiliation: Department of Biochemistry, Faculty of Science, P. J. Šafárik University, Moyzesova 11, SK-041 54 Košice, Slovak Republic.
authors.forename: Júlia
authors.initials: J
authors.lastname: Kudláčová
authors.affiliation: Department of Biochemistry and Microbiology, Slovak University of Technology, Radlinského 9, SK-812 37 Bratislava, Slovak Republic.
authors.forename: Helena
authors.initials: H
authors.lastname: Paulíková
authors.affiliation: Department of Biochemistry and Microbiology, Slovak University of Technology, Radlinského 9, SK-812 37 Bratislava, Slovak Republic.
authors.forename: Daniela
authors.initials: D
authors.lastname: Hudecová
authors.affiliation: Department of Biochemistry and Microbiology, Slovak University of Technology, Radlinského 9, SK-812 37 Bratislava, Slovak Republic.
authors.forename: Veronika
authors.initials: V
authors.lastname: Helebrandtová
authors.affiliation: Department of Inorganic Chemistry, Faculty of Science, P. J. Šafárik University, Moyzesova 11, SK-041 54 Košice, Slovak Republic.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Almáši
authors.affiliation: NMR Laboratory, Faculty of Science, P. J. Šafárik University, Moyzesova 11, SK-041 54 Košice, Slovak Republic.
authors.forename: Mária
authors.initials: M
authors.lastname: Vilková
authors.affiliation: Institute of Physics of the Czech Academy of Sciences, Na Slovance 2, CZ-18221 Praha 8, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Dušek
authors.affiliation: Department of Inorganic Chemistry, Faculty of Science, P. J. Šafárik University, Moyzesova 11, SK-041 54 Košice, Slovak Republic.
authors.forename: Dáša
authors.initials: D
authors.lastname: Bobáľová
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D026942:DNA Topoisomerases / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005998:Glycine / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D051379:Mice; D009536:Niacinamide / Q000737:chemistry*; D012834:Silver / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D056831:Coordination Complexes; D009536:Niacinamide; D012834:Silver; D004247:DNA; D026942:DNA Topoisomerases; D005998:Glycine
keywords: Antimicrobial effect; Cytotoxicity; Intercalation; Silver complex; Stability; Topo I and II inhibition assay