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Trávníček, Zdeněk; Štarha, Pavel; Vančo, Ján; Šilha, Tomáš; Hošek, Jan; Suchý, Pavel; Pražanová, Gabriela
Journal of medicinal chemistry, 05/2012, Letnik: 55, Številka: 10Journal Article
The gold(I) complexes of the general formula Au(L n )(PPh3)·xH2O (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.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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