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dc.contributor.authorStrydom, Belinda
dc.contributor.authorMalan, Sarel F.
dc.contributor.authorBergh, Jacobus J.
dc.contributor.authorPetzer, Jacobus P.
dc.contributor.authorCastagnoli, Neal
dc.date.accessioned2016-02-04T12:23:01Z
dc.date.available2016-02-04T12:23:01Z
dc.date.issued2010
dc.identifier.citationStrydom, B. et al. 2010. Inhibition of monoamine oxidase by 8-benzyloxycaffeine analogues. Bioorganic & medicinal chemistry, 18(3):1018-1028. [https://doi.org/10.1016/j.bmc.2009.12.064]en_US
dc.identifier.issn0968-0896
dc.identifier.urihttp://hdl.handle.net/10394/16151
dc.identifier.urihttps://www.sciencedirect.com/science/article/pii/S0968089609011560
dc.identifier.urihttps://doi.org/10.1016/j.bmc.2009.12.064
dc.descriptionSupplementary data associated with this article can be found, in the online version, at doi:10.1016/j.bmc.2009.12.064.en_US
dc.description.abstractBased 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 lM for the inhibition of human MAO-A, and 0.023– 0.59 lM 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 (p) and Hammett electronic (r) 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.en_US
dc.description.sponsorshipNational Research Foundation; Medical Research Council, South Africa.en_US
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.subjectMonoamine oxidaseen_US
dc.subjectReversible inhibitionen_US
dc.subject8-Benzyloxycaffeineen_US
dc.subjectCaffeineen_US
dc.subjectQuantitative structure-activity relationshipen_US
dc.subjectMolecular dockingen_US
dc.titleInhibition of monoamine oxidase by 8-benzyloxycaffeine analoguesen_US
dc.typeArticleen_US
dc.contributor.researchID10199667 - Malan, Sarel Francois
dc.contributor.researchID10727388 - Petzer, Jacobus Petrus
dc.contributor.researchID10057072 - Bergh, Jacobus Johannes
dc.contributor.researchID12989169 - Strydom, Belinda


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