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dc.contributor.authorVan der Walt, Elizna M.en_US
dc.contributor.authorBergh, Jacobus J.en_US
dc.contributor.authorPetzer, Jacobus P.en_US
dc.contributor.authorMalan, Sarel F.en_US
dc.contributor.authorMilczek, E.M.
dc.date.accessioned2010-08-04T15:36:05Z
dc.date.available2010-08-04T15:36:05Z
dc.date.issued2009en_US
dc.identifier.citationVan der Walt, E.M. et al. 2009. Inhibition of monoamine oxidase by E-styrylisatin analogues. Bioorganic & medicinal chemistry letters, 19(9):2509-2513. [https://doi.org/10.1016/j.bmcl.2009.03.030]en_US
dc.identifier.issn0968-0896
dc.identifier.urihttp://hdl.handle.net/10394/3358
dc.identifier.urihttps://doi.org/10.1016/j.bmcl.2009.03.030
dc.identifier.urihttp://www.sciencedirect.com/science/article/pii/S0960894X09003503
dc.description.abstractPrevious studies have shown that (E)-8-(3-chlorostyryl)caffeine (CSC) is a specific reversible inhibitor of human monoamine oxidase B (MAO-B) and does not bind to human MAO-A. Since the small molecule isatin is a natural reversible inhibitor of both MAO-B and MAO-A, (E)-5-styrylisatin and (E)-6-styrylisatin analogues were synthesized in an attempt to identify inhibitors with enhanced potencies and specificities for MAO-B. The (E)-styrylisatin analogues were found to exhibit higher binding affinities than isatin with the MAO preparations tested. The (E)-5-styrylisatin analogues bound more tightly than the (E)-6 analogue although the latter exhibits the highest MAO-B selectivity. Molecular docking studies with MAO-B indicate that the increased binding affinity exhibited by the (E)-styrylisatin analogues, in comparison to isatin, is best explained by the ability of the styrylisatins to bridge both the entrance cavity and the substrate cavity of the enzyme. Experimental support for this model is shown by the weaker binding of the analogues to the Ile199Ala mutant of human MAO-B. The lower selectivity of the (E)-styrylisatin analogues between MAO-A and MAO-B, in contrast to CSC, is best explained by the differing relative geometries of the aromatic rings for these two classes of inhibitors.
dc.publisherElsevier
dc.subjectMonoamine oxidase A
dc.subjectMonoamine oxidase B
dc.subjectReversible inhibitor
dc.subjectIsatin
dc.subject(E)-5-Styrylisatin
dc.subject(E)-6-Styrylisatin
dc.titleInhibition of monoamine oxidase by E-styrylisatin analoguesen_US
dc.contributor.researchID10057072 - Bergh, Jacobus Johannes
dc.contributor.researchID10727388 - Petzer, Jacobus Petrus
dc.contributor.researchID10199667 - Malan, Sarel Francois


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