4.6 Article

New silver complexes with bioactive glycine and nicotinamide molecules - Characterization, DNA binding, antimicrobial and anticancer evaluation

Journal

JOURNAL OF INORGANIC BIOCHEMISTRY
Volume 168, Issue -, Pages 1-12

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.jinorgbio.2016.12.003

Keywords

Silver complex; Antimicrobial effect; Stability; Cytotoxicity; Intercalation; Topo I and II inhibition assay

Funding

  1. Slovak Research and Development Agency [APVV-15-0520]
  2. Ministry of Education, Science, Research
  3. Sport of the Slovak Republic [VEGA 1/0001/13, VEGA 1/0131/16, KEGA 002UPJS-4/2015]

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This study introduces a pair of newly synthesized silver complexes, [Ag-2(HGly)(2)] (NO3)(2n) (1) and [Ag(Nam)(2)]NO3 center dot 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 by H-1 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 Agl-Ag2 distance of 2.8018(6) angstrom. 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 coil) 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 Chi 10(3) to 20.34 Chi 103 M-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 2 mu M.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. (C) 2016 Elsevier Inc. All rights reserved.

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