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dc.contributor.authorOgunrombi, Modupe O.
dc.contributor.authorMalan, Sarel F.
dc.contributor.authorTerre'Blanche, Gisella
dc.contributor.authorBergh, Jacobus J.
dc.contributor.authorPetzer, Jacobus P.
dc.identifier.citationOgunrombi, M.O. et al. 2008. Structure-activity relationships in the inhibition of monoamine oxidase B by 1-methyl-3-phenylpyrroles. Bioorganic & medicinal chemistry, 16(5):2463-2472. []en
dc.identifier.issn0968-0896 (Online)
dc.description.abstract1-Methyl-3-phenyl-3-pyrrolines are structural analogues of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and like MPTP are selective substrates of monoamine oxidase B (MAO-B). As part of an ongoing investigation into the substrate properties of various 1-methyl-3-phenyl-3-pyrrolinyl derivatives, it is shown in the present study that their respective MAO-B catalyzed oxidation products act as reversible competitive inhibitors of the enzyme. The most potent inhibitor among the oxidation products considered was 1-methyl-3-(4-trifluoromethylphenyl)pyrrole with an enzyme-inhibitor dissociation constant (Ki value) of 1.30 μM. The least potent inhibitor was found to be 1-methyl-3-phenylpyrrole with a Ki value of 118 μM. The results of an SAR study established that the potency of MAO-B inhibition by the 1-methyl-3-phenylpyrrolyl derivatives examined here is dependent on the Taft steric parameter (Es) and Swain–Lupton electronic constant (F) of the substituents attached to C-4 of the phenyl ring. Electron-withdrawing substituents with a large degree of steric bulkiness appear to enhance inhibition potency. Potency was also found to vary with the substituents at C-3, again with Es and F being the principal substituent descriptors
dc.subjectMonoamine oxidase B
dc.subjectReversible inhibitors
dc.subjectCompetitive inhibition
dc.subjectStructure-activity relationship
dc.titleStructure-activity relationships in the inhibition of monoamine oxidase B by 1-methyl-3-phenylpyrrolesen
dc.contributor.researchID10057072 - Bergh, Jacobus Johannes
dc.contributor.researchID10199667 - Malan, Sarel Francois
dc.contributor.researchID10727388 - Petzer, Jacobus Petrus
dc.contributor.researchID10206280 - Terre'Blanche, Gisella
dc.contributor.researchID12608351 - Ogunrombi, Modupe Olufunmilayo

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