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dc.contributor.authorPetzer, Anél
dc.contributor.authorGrobler, Paul
dc.contributor.authorBergh, Jacobus J.
dc.contributor.authorPetzer, Jacobus P.
dc.date.accessioned2016-02-11T08:59:34Z
dc.date.available2016-02-11T08:59:34Z
dc.date.issued2014
dc.identifier.citationPetzer, A. et al. 2014. Inhibition of monoamine oxidase by selected phenylalkylcaffeine analogues. Journal of pharmacy and pharmacology, 66(5):677-687. [https://doi.org/10.1111/jphp.12193]en_US
dc.identifier.issn0022-3573
dc.identifier.issn2042-7158 (Online)
dc.identifier.urihttp://hdl.handle.net/10394/16259
dc.identifier.urihttps://onlinelibrary.wiley.com/doi/abs/10.1111/jphp.12193
dc.identifier.urihttps://doi.org/10.1111/jphp.12193
dc.description.abstractObjectives Caffeine represents a useful scaffold for the design of monoamine oxidase (MAO) type B inhibitors. Specifically, substitution on the C8 position yields structures which are high-potency MAO-B inhibitors. To explore the structure–activity relationships of MAO-B inhibition by caffeine-derived compounds, this study examines the MAO inhibitory properties of a series of phenylalkylcaffeine analogues. Methods Employing the recombinant human enzymes, the potencies (IC50 values) by which the caffeine analogues inhibit MAO-A and MAO-B were measured. The reversibility of inhibition of a selected inhibitor was determined by measuring the recovery of enzyme activity after dilution and dialysis of enzymeinhibitor mixtures. Key findings The results document that the phenylalkylcaffeine analogues are reversible and selective MAO-B inhibitors with a competitive mode of inhibition. The most potent analogue, 8-(7-phenylheptyl)caffeine, exhibits IC50 values for the inhibition of MAO-A and MAO-B of 3.01 μm and 0.086 μm, respectively. Increasing the length of the alkyl side chain leads to enhanced MAO-A and MAO-B inhibitory potency while introduction of a carbonyl group reduces MAO-B inhibitory potency. Conclusions Phenylalkylcaffeines represent a new class of high-potency MAO-B inhibitors with the longer alkyl side chains yielding enhanced inhibitory activity. Such compounds may represent useful leads for the development of antiparkinsonian therapiesen_US
dc.description.sponsorshipSupported in part by the Medical Research Council and National Research Foundation (NRF) of South Africa (Grant specific unique reference numbers (UID) 85642 and 80647)en_US
dc.language.isoenen_US
dc.publisherWileyen_US
dc.subjectCaffeineen_US
dc.subjectCompetitiveen_US
dc.subjectMonoamine oxidaseen_US
dc.subjectReversible inhibitionen_US
dc.subjectStructure-activity relationshipen_US
dc.titleInhibition of monoamine oxidase by selected phenylalkylcaffeine analoguesen_US
dc.typeArticleen_US
dc.contributor.researchID10727388 - Petzer, Jacobus Petrus
dc.contributor.researchID12264954 - Petzer, Anél
dc.contributor.researchID10057072 - Bergh, Jacobus Johannes
dc.contributor.researchID20069162 - Grobler, Paul Johan


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