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

J Inorg Biochem. 2017 Mar:168:1-12. doi: 10.1016/j.jinorgbio.2016.12.003. Epub 2016 Dec 15.

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 by 1H 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 2.01×103 to 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.

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Infective Agents / chemistry
  • Anti-Infective Agents / pharmacology
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Bacteria / drug effects*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology*
  • Crystallography, X-Ray
  • DNA / chemistry
  • DNA / metabolism*
  • DNA Topoisomerases / metabolism
  • Enzyme Activation / drug effects
  • Glycine / chemistry*
  • Inhibitory Concentration 50
  • Mice
  • Niacinamide / chemistry*
  • Silver / chemistry
  • Silver / pharmacology*

Substances

  • Anti-Infective Agents
  • Antineoplastic Agents
  • Coordination Complexes
  • Niacinamide
  • Silver
  • DNA
  • DNA Topoisomerases
  • Glycine