Thio- and aminocaffeine analogues as inhibitors of human monoamine oxidase

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dc.contributor.author Bergh, Jacobus Johannes
dc.contributor.author Booysen, Hermanus Perold
dc.contributor.author Moraal, Christina Maria
dc.contributor.author Petzer, Jacobus Petrus
dc.contributor.author Petzer, Anél
dc.contributor.author Terre'Blanche, Gisella
dc.date.accessioned 2012-09-11T09:44:12Z
dc.date.available 2012-09-11T09:44:12Z
dc.date.issued 2011
dc.identifier.citation Booysen, H.P. et al. 2011. Thio- and aminocaffeine analogues as inhibitors of human monoamine oxidase. Bioorganic & Medicinal Chemistry, 19(24):7507-7518. [http://www.journals.elsevier.com/bioorganic-and-medicinal-chemistry] en_US
dc.identifier.issn 0968-0896
dc.identifier.issn 1464-3391 (Online)
dc.identifier.uri http://hdl.handle.net/10394/7380
dc.description.abstract In a recent study it was shown that 8-benzyloxycaffeine analogues act as potent reversible inhibitors of human monoamine oxidase (MAO) A and B. Although the benzyloxy side chain appears to be particularly favorable for enhancing the MAO inhibition potency of caffeine, a variety of other C8 oxy substituents of caffeine also lead to potent MAO inhibition. In an attempt to discover additional C8 substituents of caffeine that lead to potent MAO inhibition and to explore the importance of the ether oxygen for the MAO inhibition properties of C8 oxy-substituted caffeines, a series of 8-sulfanyl- and 8-aminocaffeine analogues were synthesized and their human MAO-A and -B inhibition potencies were compared to those of the 8-oxycaffeines. The results document that the sulfanylcaffeine analogues are reversible competitive MAO-B inhibitors with potencies comparable to those of the oxycaffeines. The most potent inhibitor, 8-{[(4-bromophenyl)methyl]sulfanyl}caffeine, exhibited an IC50 value of 0.167 lM towards MAO-B. While the sulfanylcaffeine analogues also exhibit affinities for MAO-A, they display in general a high degree of MAO-B selectivity. The aminocaffeine analogues, in contrast, proved to be weak MAO inhibitors with a number of analogues exhibiting no binding to the MAO-A and -B isozymes. The results of this study are discussed with reference to possible binding orientations of selected caffeine analogues within the active site cavities of MAO-A and -B. MAO-B selective sulfanylcaffeine derived inhibitors may act as lead compounds for the design of antiparkinsonian therapies. en_US
dc.description.uri http://dx.doi.org/10.1016/j.bmc.2011.10.036
dc.language.iso en en_US
dc.publisher Elsevier en_US
dc.subject Monoamine oxidase en_US
dc.subject reversible inhibition en_US
dc.subject caffeine en_US
dc.subject sulfanylcaffeine en_US
dc.subject thiocaffeine en_US
dc.subject aminocaffeine en_US
dc.title Thio- and aminocaffeine analogues as inhibitors of human monoamine oxidase en_US
dc.type Article en_US

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