• Login
    View Item 
    •   NWU-IR Home
    • Research Output
    • Faculty of Health Sciences
    • View Item
    •   NWU-IR Home
    • Research Output
    • Faculty of Health Sciences
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Dual inhibition of monoamine oxidase B and antagonism of the adenosine A2A receptor by (E,E)-8-(4phenylbytadien-1-yl) caffeine analogues

    Thumbnail
    Date
    2008
    Author
    Malan, Sarel F.
    Bergh, Jacobus J.
    Petzer, Jacobus P.
    Castagnoli, Neal
    Pretorius, Judey
    Metadata
    Show full item record
    Abstract
    The adenosine A2A receptor has emerged as an attractive target for the treatment of Parkinson’s disease (PD). Evidence suggests that antagonists of the A2A receptor (A2A antagonists) may be neuroprotective and may help to alleviate the symptoms of PD. We have reported recently that several members of the (E)-8-styrylcaffeine class of A2A antagonists also are potent inhibitors of monoamine oxidase B (MAO-B). Since MAO-B inhibitors are known to possess anti-parkinsonian properties, dual-target-directed drugs that block both MAO-B and A2A receptors may have enhanced value in the management of PD. In an attempt to explore this concept further we have prepared three additional classes of C-8 substituted caffeinyl analogues. The 8-phenyl- and 8-benzylcaffeinyl analogues exhibited relatively weak MAO-B inhibition potencies while selected (E,E)-8-(4-phenylbutadien-1-yl)caffeinyl analogues were found to be exceptionally potent reversible MAO-B inhibitors with enzyme–inhibitor dissociation constants (Ki values) ranging from 17 to 149 nM. Furthermore, these (E,E)-8-(4-phenylbutadien-1-yl)caffeines acted as potent A2A antagonists with Ki values ranging from 59 to 153 nM. We conclude that the (E,E)-8-(4-phenylbutadien-1-yl)caffeines are a promising candidate class of dual-acting compounds.
    URI
    http://hdl.handle.net/10394/2684
    https://www.sciencedirect.com/science/article/pii/S0968089608007141
    https://doi.org/10.1016/j.bmc.2008.07.088
    Collections
    • Faculty of Health Sciences [2368]

    Copyright © North-West University
    Contact Us | Send Feedback
    Theme by 
    Atmire NV
     

     

    Browse

    All of NWU-IR Communities & CollectionsBy Issue DateAuthorsTitlesSubjectsAdvisor/SupervisorThesis TypeThis CollectionBy Issue DateAuthorsTitlesSubjectsAdvisor/SupervisorThesis Type

    My Account

    LoginRegister

    Copyright © North-West University
    Contact Us | Send Feedback
    Theme by 
    Atmire NV