LASSBio-468: a new achiral thalidomide analogue which modulates TNF- and NO production and inhibits endotoxic shock and arthritis in an animal model
As part of a program researching the synthesis and immunopharmacological evaluation of novel synthetic compounds, we have described the immune modulatory profile of the new achiral thalidomide analogue LASSBio-468 in the present work. This compound was planned as an N-substituted phthalimide derivat...
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Veröffentlicht in: | International immunopharmacology 2005-03, Vol.5 (3), p.485-494 |
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Hauptverfasser: | , , , , , , , |
Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | As part of a program researching the synthesis and immunopharmacological evaluation of novel synthetic compounds, we have described the immune modulatory profile of the new achiral thalidomide analogue LASSBio-468 in the present work. This compound was planned as an N-substituted phthalimide derivate, structurally designed as a hybrid of thalidomide and aryl sulfonamides, which were previously described as tumor necrosis factor-alpha (TNF-) and PDE4 inhibitors. LASSBio-468 was recently demonstrated to inhibit the TNF- production induced by lipopolysaccharide (LPS), in vivo. Here, we investigated whether this compound would affect chronic inflammation processes associated with the production of this pro-inflammatory cytokine. Treatment with LASSBio-468 before a lethal dose injection of LPS in animals greatly inhibited endotoxic shock. This effect seems to be mediated by a specific down regulation of TNF- and nitric oxide production, regulated mainly at the RNA level. In another model, histopathological analysis indicated that this compound also inhibited adjuvant-induced arthritis in rats. Taken together, our data demonstrated a potent anti-inflammatory effect of LASSBio-468, suggesting its use as a potential drug against chronic inflammatory diseases. |
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ISSN: | 1567-5769 |
DOI: | 10.1016/j.intimp.2004.10.017 |