• myGriffith
    • Staff portal
    • Contact Us⌄
      • Future student enquiries 1800 677 728
      • Current student enquiries 1800 154 055
      • International enquiries +61 7 3735 6425
      • General enquiries 07 3735 7111
      • Online enquiries
      • Staff phonebook
    View Item 
    •   Home
    • Griffith Research Online
    • Journal articles
    • View Item
    • Home
    • Griffith Research Online
    • Journal articles
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

  • All of Griffith Research Online
    • Communities & Collections
    • Authors
    • By Issue Date
    • Titles
  • This Collection
    • Authors
    • By Issue Date
    • Titles
  • Statistics

  • Most Popular Items
  • Statistics by Country
  • Most Popular Authors
  • Support

  • Contact us
  • FAQs
  • Admin login

  • Login
  • Natural Products, Stylissadines A and B, Specific Antagonists of the P2X7 Receptor, an Important Inflammatory Target

    Author
    Buchanan, Malcolm
    Carroll, Anthony
    Addepalli, Rama
    Avery, Vicky
    N. A. Hooper, John
    Quinn, Ronald
    Year published
    2007
    Metadata
    Show full item record
    Abstract
    The distribution of the P2X7 receptor in inflammatory cells suggests that P2X7 antagonists have a significant role to play in the treatment of inflammatory disease. We conducted a natural product high-throughput screening campaign to discover P2X7 receptor antagonists. The Australian marine sponge Stylissa flabellata yielded two new bisimidazo-pyrano-imidazole bromopyrrole ether alkaloids, stylissadines A (IC50 0.7 uM) and B (IC50 1.8 uM), as the specific bioactive constituents. The compounds inhibit BzATP-mediated pore formation in THP-1 cells. Also present in this extract was considerable nonspecific bioactivity in the hemeolysin specificity assay. A new pyrrole-imidazole alkaloid, konbu'acidin B, and the known pyrrole-imidazole alkaloids 4,5-dibromopalau'amine and massadine were also isolated and had nonspecific activity. ROESY and proton coupling constant data indicated that the stereochemistry at C12, C17, and C20 in 4,5-dibromopalau'amine should be revised to 12R, 17S, 20S. By analogy, the relative stereochemistry of palau'amine, 4-bromopalau'amine, styloguanidine, 3-bromostyloguanidine, and 2,3-dibromostyloguanidine should also be revised to 12R, 17S, 20S. Stylissadines A and B are the most potent natural product P2X7 antagonists to be isolated to date and provide a novel class of P2X7 receptor inhibitors. They are also the first examples of tetrameric pyrrole-imidazole alkaloids.
    Journal Title
    Journal of Organic Chemistry
    Volume
    72
    Issue
    7
    Publisher URI
    http://pubs.acs.org/journals/joceah/index.html
    DOI
    https://doi.org/10.1021/jo062007q
    Copyright Statement
    © 2007 American Chemical Society. Self-archiving of the author-manuscript version is not yet supported by this publisher. The contents of this journal can be freely accessed online via the ACS web page after publication. Use hypertext link above to access the ACS website.
    Publication URI
    http://hdl.handle.net/10072/17694
    Collection
    • Journal articles

    Footer

    Social media

    • Facebook
    • Twitter
    • YouTube
    • Instagram
    • Linkedin
    First peoples of Australia
    • Aboriginal
    • Torres Strait Islander

    Disclaimer

    • Privacy policy
    • Copyright matters
    • CRICOS Provider - 00233E

    Tagline

    • Gold Coast
    • Logan
    • Brisbane
    • Australia