dc.contributor.author | Petzer, Anél | |
dc.contributor.author | Grobler, Paul | |
dc.contributor.author | Bergh, Jacobus J. | |
dc.contributor.author | Petzer, Jacobus P. | |
dc.date.accessioned | 2016-02-11T08:59:34Z | |
dc.date.available | 2016-02-11T08:59:34Z | |
dc.date.issued | 2014 | |
dc.identifier.citation | Petzer, 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.issn | 0022-3573 | |
dc.identifier.issn | 2042-7158 (Online) | |
dc.identifier.uri | http://hdl.handle.net/10394/16259 | |
dc.identifier.uri | https://onlinelibrary.wiley.com/doi/abs/10.1111/jphp.12193 | |
dc.identifier.uri | https://doi.org/10.1111/jphp.12193 | |
dc.description.abstract | Objectives 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
therapies | en_US |
dc.description.sponsorship | Supported 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.iso | en | en_US |
dc.publisher | Wiley | en_US |
dc.subject | Caffeine | en_US |
dc.subject | Competitive | en_US |
dc.subject | Monoamine oxidase | en_US |
dc.subject | Reversible inhibition | en_US |
dc.subject | Structure-activity relationship | en_US |
dc.title | Inhibition of monoamine oxidase by selected phenylalkylcaffeine analogues | en_US |
dc.type | Article | en_US |
dc.contributor.researchID | 10727388 - Petzer, Jacobus Petrus | |
dc.contributor.researchID | 12264954 - Petzer, Anél | |
dc.contributor.researchID | 10057072 - Bergh, Jacobus Johannes | |
dc.contributor.researchID | 20069162 - Grobler, Paul Johan | |