• 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.

    Inhibition of  monoamine oxidase by 8-benzyloxycaffeine analogues

    Thumbnail
    Date
    2010
    Author
    Strydom, Belinda
    Malan, Sarel F.
    Bergh, Jacobus J.
    Petzer, Jacobus P.
    Castagnoli, Neal
    Metadata
    Show full item record
    Abstract
    Based on recent reports that several (E)-8-styrylcaffeinyl analogues are potent reversible inhibitors of monoamine oxidase B (MAO-B), a series of 8-benzyloxycaffeinyl analogues were synthesized and evaluated as inhibitors of baboon liver MAO-B and recombinant human MAO-A and -B. The 8-benzyloxycaffeinyl analogues were found to inhibit reversibly both MAO isoforms with enzyme–inhibitor dissociation constants (Ki values) ranging from 0.14 to 1.30 μM for the inhibition of human MAO-A, and 0.023–0.59 μM for the inhibition of human MAO-B. The most potent MAO-A inhibitor was 8-(3-methylbenzyloxy)caffeine while 8-(3-bromobenzyloxy)caffeine was the most potent MAO-B inhibitor. The analogues inhibited human and baboon MAO-B with similar potencies. A quantitative structure–activity relationship (QSAR) study indicated that the MAO-B inhibition potencies of the 8-benzyloxycaffeinyl analogues are dependent on the Hansch lipophilicity (π) and Hammett electronic (σ) constants of the substituents at C-3 of the benzyloxy ring. Electron-withdrawing substituents with a high degree of lipophilicity enhance inhibition potency. These results are discussed with reference to possible binding orientations of the inhibitors within the active site cavities of MAO-A and -B
    URI
    http://hdl.handle.net/10394/5998
    https://www.sciencedirect.com/science/article/pii/S0968089609011560
    https://doi.org/10.1016/j.bmc.2009.12.064
    Collections
    • Faculty of Health Sciences [2369]

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

     

    Browse

    All of NWU-IR Communities & CollectionsBy Issue DateAuthorsTitlesSubjectsAdvisorThis CollectionBy Issue DateAuthorsTitlesSubjectsAdvisor

    My Account

    LoginRegister

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