Diverse in vitro and in vivo anti-inflammatory effects of trichlorido-gold(III) complexes with N6-benzyladenine derivatives

J Inorg Biochem. 2014 May:134:92-9. doi: 10.1016/j.jinorgbio.2014.02.002. Epub 2014 Feb 14.

Abstract

A series of gold(III) complexes involving differently substituted derivatives of a plant hormone N6-benzyladenine (HL1-5) is reported. The complexes have the general formula [Au(HL1-5)Cl3]∙nH2O (n=0 for 1, 3-5; and n=1 for 2), where N6-(2-fluorobenzyl)adenine (HL1), N6-(2-chlorobenzyl)adenine (HL2), N6-(3-chlorobenzyl)adenine (HL3), N6-(4-chlorobenzyl)adenine (HL4) and N6-(4-methylbenzyl)adenine (HL5) represent the N9-coordinated ligands. The results of thorough characterization (elemental and thermal analyses, FT-IR, Raman and NMR spectroscopies, ESI+ mass spectrometry, conductivity measurements, DFT calculations) showed that the presented complexes 1-5 involve a central gold(III) atom coordinated in a square-planar geometry by the N9 atom of the purine moiety of HL1-5 and by three chlorido ligands. The complexes (1-5) were studied in vitro for cytotoxicity and anti-inflammatory activity on LPS-activated macrophages (THP-1 cell line), and in vivo for anti-inflammatory effects (1, 2, 5) using the carrageenan-induced hind paw oedema model on rats. Surprisingly, the results on the in vitro level revealed that the complexes show negligible cytotoxicity and anti-inflammatory activity, however, the activity on the in vivo level was found to be significant, fully comparable with the utilized drug Indomethacin, or even better as compared to a gold-containing metallodrug Auranofin.

Keywords: Adenine derivatives; Anti-inflammatory; Cytotoxicity; Gold(III) complexes; TNF-α.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Auranofin / pharmacology
  • Benzyl Compounds
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chlorides / chemistry*
  • Coordination Complexes / chemical synthesis
  • Coordination Complexes / pharmacology*
  • Edema / drug therapy
  • Edema / pathology
  • Gold / chemistry*
  • Hindlimb
  • Humans
  • Indomethacin / pharmacology
  • Kinetin / chemistry*
  • Ligands
  • Male
  • Monocytes / cytology
  • Monocytes / drug effects
  • Purines
  • Rats
  • Rats, Wistar

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Benzyl Compounds
  • Chlorides
  • Coordination Complexes
  • Ligands
  • Purines
  • Auranofin
  • Gold
  • benzylaminopurine
  • Kinetin
  • Indomethacin