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dc.contributor.authorVan Der Walt, Elizna Magdalenaen_US
dc.contributor.authorBergh, Jacobusen_US
dc.contributor.authorPetzer, Jacobusen_US
dc.contributor.authorMalan, Sarelen_US
dc.contributor.authorCastagnoli, N Jr
dc.contributor.authorMilczek, E M
dc.contributor.authorEdmondsonb, Dale E
dc.identifier.citationVAN DER WALT, E.M., BERGH, J., PETZER, J., MALAN, S., CASTAGNOLI, N. Jr., MILCZEK, E. M., & Edmondsonb, D.L. 2009. Inhibition of monoamine oxidase by E_-styrylisatin analogues. Bioorganic and Medicinal Chemistry Letters, 19(9):2509-2513, May []en_US
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 Ltd
dc.titleInhibition of monoamine oxidase by E_-styrylisatin analoguesen_US

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