Anti-inflammatory Active Gold(I) Complexes Involving 6-Substituted-Purine Derivatives

Abstract

The gold(I) complexes of the general formula [Au(L(n))(PPh(3))]·xH(2)O (1-8; n = 1-8 and x = 0-1.5), where L(n) stands for a deprotonated form of the benzyl-substituted derivatives of 6-benzylaminopurine, were prepared, thoroughly characterized (elemental analyses, FT-IR, Raman and multinuclear NMR spectroscopy, ESI+ mass spectrometry, conductivity, DFT calculations), and studied for their in vitro cytotoxicity and in vitro and in vivo anti-inflammatory effects on LPS-activated macrophages (derived from THP-1 cell line) and using the carrageenan-induced hind paw edema model on rats. The obtained results indicate that the representative complexes (1, 3, 6) exhibit a strong ability to reduce the production of pro-inflammatory cytokines TNF-α, IL-1β and HMGB1 without influence on the secretion of anti-inflammatory cytokine IL-1RA in the LPS-activated macrophages. The complexes also significantly influence the formation of edema, caused by the intraplantar application of polysaccharide λ-carrageenan to rats in vivo. All the tested complexes showed similar or better biological effects as compared with Auranofin, but contrary to Auranofin they were found to be less cytotoxic in vitro. The obtained results clearly indicate that the gold(I) complexes behave as very effective anti-inflammatory agents and could prove to be useful for the treatment of difficult to treat inflammatory diseases such as rheumatoid arthritis.

Gold(I)-Triphenylphosphine Complexes with Hypoxanthine-Derived Ligands: In Vitro Evaluations of Anticancer and Anti-Inflammatory Activities

“…L-cysteine and reduced glutathione) were studied by means of mass spectrometry. Moreover, this work fits within the focus of our long term study dedicated to research and development of new transition metal complexes showing various types of biological effects, represented dominantly by the anticancer {Pt(II) [23], Pd(II) [24], Cu(II) [25], [26] or Ru(III) [27]}, anti-inflammatory {Au(I/III)} [15], [16], [28], antidiabetic and cytoprotective {Cu(II) [29]} activities.…”

“…Among linear gold(I) phosphine complexes, those involving ligands as e.g. dithiocarbamates [1], sulfanylpropenoates [11], naphthalimide derivatives [12], imidazole, pyrazole [13], [14] as well as purine derivatives [15], [16] have been investigated. It has been established that the gold(I)-phosphine moiety is responsible for the actual interactions [3], [17] with the target sites of the biological molecules, i.e.…”

“…mostly the selanyl-groups of enzymes [1], [18], while the other, weaker bonded ligand influences the kinetic profile of the compounds. This principle has been employed by our group in several recently published works, describing highly antitumor active as well as anti-inflammatory potent gold(I) complexes of the type [Au(L)(PPh 3 )] involving various N 6-benzyladenine derivatives (L) [15], [16].…”

Synthesis, characterization, cytotoxic and antitubercular activities of new gold(I) and gold(III) complexes containing ligands derived from carbohydrates

“…Other biological activities for these compounds have also been reported. For instance, antiinflammatory (Trávnicek et al 2012) and antiparasitic activities (Navarro 2009). …”

Dichlorido-platinum(II) complexes with kinetin derivatives as promising cytotoxic agents avoiding resistance of cancer cells: Contrasting results between cisplatin and oxaliplatin analogues

“…The cytokinins and their synthetic derivatives, having their intrinsic bio-activity, can be advantageously exploited in the preparation and study of significantly biologically active complexes, in which these organic compounds act as N-donor ligands coordinated to a suitable transition metal. Indeed, this approach has already resulted in identification of complexes possessing significant in vitro as well as in vivo anti-tumour [16,17,18], anti-inflammatory [19,20] and antidiabetic [21] activity. Concretely, the studies focused on platinum(II) complexes involving various N6-benzyladenines as N-donor carrier ligands in combination with different leaving groups, i.e.…”