dc.contributor.author | Strydom, Belinda | |
dc.contributor.author | Bergh, Jacobus J. | |
dc.contributor.author | Petzer, Jacobus P. | |
dc.date.accessioned | 2012-10-04T06:50:47Z | |
dc.date.available | 2012-10-04T06:50:47Z | |
dc.date.issued | 2011 | |
dc.identifier.citation | Strydom, B. et al. 2011. 8-Aryl- and alkyloxycaffeine analogues as inhibitors of monoamine oxidase. European journal of medicinal chemistry, 46(8):3474-3485. [https://doi.org/10.1016/j.ejmech.2011.05.014] | en_US |
dc.identifier.issn | 0223-5234 | |
dc.identifier.issn | 1768-3254 (Online) | |
dc.identifier.uri | http://hdl.handle.net/10394/7436 | |
dc.identifier.uri | https://www.sciencedirect.com/science/article/pii/S022352341100376X | |
dc.identifier.uri | https://doi.org/10.1016/j.ejmech.2011.05.014 | |
dc.description | Published under the auspices of the French Société de Chimie Thérapeutique (SCT) | en_US |
dc.description.abstract | Recently it was reported that a series of 8-benzyloxycaffeine analogues are potent reversible inhibitors of human monoamine oxidase (MAO) A and B. In an attempt to discover additional C8 oxy substituents of caffeine that lead to potent MAO inhibition, a series of related 8-aryl- and alkyloxycaffeine analogues were synthesized and their MAO-A and -B inhibition potencies were compared to those of the 8-benzyloxycaffeines. The results document that while the 8-substituted-oxycaffeine analogues inhibited both human MAO isoforms, they displayed a high degree of selectivity for MAO-B. 8-(3-Phenylpropoxy)caffeine, 8-(2-phenoxyethoxy)caffeine and 8-[(5-methylhexyl)oxy]caffeine were found to be the especially potent MAO-B inhibitors with IC50 values ranging from 0.38 to 0.62 μM. These inhibitors are therefore 2.5–4.6 fold more potent MAO-B inhibitors than is 8-benzyloxycaffeine (IC50 = 1.77 μM). It is also demonstrated that, analogous to 8-benzyloxycaffeine, halogen substitution on the phenyl ring of the C8 substituent significantly enhances MAO binding affinity. For example, the most potent MAO-B inhibitor of the present series is 8-[2-(4-bromophenoxy)ethoxy]caffeine with an IC50 value of 0.166 μM. This study also reports possible binding orientations of selected oxy caffeines within the active site cavities of MAO-A and MAO-B. | en_US |
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 | 8-Aryloxycaffeine | en_US |
dc.subject | 8-Alkyloxycaffeine | en_US |
dc.subject | Caffeine | en_US |
dc.subject | Molecular docking | en_US |
dc.title | 8-Aryl- and alkyloxycaffeine analogues as inhibitors of monoamine oxidase | en_US |
dc.type | Article | en_US |
dc.contributor.researchID | 10057072 - Bergh, Jacobus Johannes | |
dc.contributor.researchID | 10727388 - Petzer, Jacobus Petrus | |
dc.contributor.researchID | 12989169 - Strydom, Belinda | |