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dc.contributor.authorStrydom, Belinda
dc.contributor.authorMalan, Sarel F.
dc.contributor.authorBergh, Jacobus J.
dc.contributor.authorPetzer, Jacobus P.
dc.contributor.authorCastagnoli, Neal
dc.identifier.citationStrydom, B. et al. 2010. Inhibition of  monoamine oxidase by 8-benzyloxycaffeine analogues. Bioorganic & medicinal chemistry, 18(3):1018-1028. []en_US
dc.description.abstractBased 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.subjectMonoamine oxidase
dc.subjectReversible inhibition
dc.subjectQuantitative structure-activity relationship
dc.subjectMolecular docking
dc.titleInhibition of  monoamine oxidase by 8-benzyloxycaffeine analoguesen_US
dc.contributor.researchID10727388 - Petzer, Jacobus Petrus
dc.contributor.researchID12989169 - Strydom, Belinda
dc.contributor.researchID10199667 - Malan, Sarel Francois
dc.contributor.researchID10057072 - Bergh, Jacobus Johannes

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