dc.contributor.author | Strydom, Belinda | |
dc.contributor.author | Malan, Sarel F. | |
dc.contributor.author | Bergh, Jacobus J. | |
dc.contributor.author | Petzer, Jacobus P. | |
dc.contributor.author | Castagnoli, Neal | |
dc.date.accessioned | 2012-02-29T09:49:49Z | |
dc.date.available | 2012-02-29T09:49:49Z | |
dc.date.issued | 2010 | en_US |
dc.identifier.citation | Strydom, 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.issn | 0968-0896 | en_US |
dc.identifier.uri | http://hdl.handle.net/10394/5998 | |
dc.identifier.uri | https://www.sciencedirect.com/science/article/pii/S0968089609011560 | |
dc.identifier.uri | https://doi.org/10.1016/j.bmc.2009.12.064 | |
dc.description.abstract | Based 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 μM for the inhibition of human MAO-A, and 0.023–0.59 μM 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 (π) and Hammett electronic (σ) 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 | |
dc.language.iso | en | |
dc.publisher | Elsevier | en_US |
dc.subject | Monoamine oxidase | |
dc.subject | Reversible inhibition | |
dc.subject | 8-Benzyloxycaffeine | |
dc.subject | Caffeine | |
dc.subject | Quantitative structure-activity relationship | |
dc.subject | Molecular docking | |
dc.title | Inhibition of monoamine oxidase by 8-benzyloxycaffeine analogues | en_US |
dc.contributor.researchID | 10727388 - Petzer, Jacobus Petrus | |
dc.contributor.researchID | 12989169 - Strydom, Belinda | |
dc.contributor.researchID | 10199667 - Malan, Sarel Francois | |
dc.contributor.researchID | 10057072 - Bergh, Jacobus Johannes | |