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dc.contributor.authorLegoabe, Lesetja J.
dc.contributor.authorPetzer, Anél
dc.contributor.authorPetzer, Jacobus P.
dc.date.accessioned2016-08-19T08:09:08Z
dc.date.available2016-08-19T08:09:08Z
dc.date.issued2015
dc.identifier.citationLegoabe, L.J. et al. 2015. The synthesis and evaluation of C7-substituted α-tetralone derivatives as inhibitors of monoamine oxidase. Chemical biology & drug design, 86(4):895-904. [https://doi.org/10.1111/cbdd.12508]en_US
dc.identifier.issn1747-0277
dc.identifier.issn1747-0285 (Online)
dc.identifier.urihttp://hdl.handle.net/10394/18329
dc.identifier.urihttps://onlinelibrary.wiley.com/doi/abs/10.1111/cbdd.12508
dc.identifier.urihttps://doi.org/10.1111/cbdd.12508
dc.description.abstractBased on a previous report that α-tetralone (3,4-dihydro-2H-naphthalen-1-one) is a promising scaffold for the design of highly potent inhibitors of the enzyme, monoamine oxidase, the present study investigates the monoamine oxidase inhibitory properties of a synthetic series of fifteen C7-substituted α-tetralone derivatives. Arylalkyloxy substitution on C7 of the α-tetralone moiety yielded compounds with high inhibition potencies toward the human monoamine oxidase-B isoform with all compounds possessing IC50 values in the submicromolar range (0.00089–0.047 μm). The C7-substituted α-tetralones also were highly potent monoamine oxidase-A inhibitors with thirteen (of fifteen) compounds possessing IC50 values in the submicromolar range (0.010–0.741 μm). The α-tetralones were, however, in each instance selective for monoamine oxidase-B over the monoamine oxidase-A isoform. Dialyses of enzyme–inhibitor mixtures show that, while a representative inhibitor acts as a reversible monoamine oxidase-A inhibitor, inhibition of monoamine oxidase-B is not readily reversed by dialysis. Using a molecular modeling approach, possible binding orientations and interactions of selected α-tetralones with the active sites of the monoamine oxidases are also proposed. This study suggests that C7-substituted α-tetralones are promising monoamine oxidase inhibitors and may represent lead compounds for the development of therapies for Parkinson's disease and depressionen_US
dc.description.sponsorshipMedical Research Council and National Research Foundation of South Africa [Grant specific unique reference numbers (UID) 85642, 80647 and 80637]en_US
dc.language.isoenen_US
dc.publisherWileyen_US
dc.subjectCompetitiveen_US
dc.subjectDialysisen_US
dc.subjectInhibitionen_US
dc.subjectMonoamine oxidaseen_US
dc.subjectReversibleen_US
dc.subjectα-Tetraloneen_US
dc.titleThe synthesis and evaluation of C7-substituted α-tetralone derivatives as inhibitors of monoamine oxidaseen_US
dc.typeArticleen_US
dc.contributor.researchID12902608 - Legoabe, Lesetja Jan
dc.contributor.researchID12264954 - Petzer, Anél
dc.contributor.researchID10727388 - Petzer, Jacobus Petrus


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