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

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.