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dc.contributor.authorMinders, Corné
dc.contributor.authorPetzer, Jacobus P.
dc.contributor.authorPetzer, Anél
dc.contributor.authorLourens, Anna C.U.
dc.date.accessioned2016-08-22T07:52:34Z
dc.date.available2016-08-22T07:52:34Z
dc.date.issued2015
dc.identifier.citationMinders, C. et al. 2015. Monoamine oxidase inhibitory activities of heterocyclic chalcones. Bioorganic & medicinal chemistry letters, 25(22):5270-5276. [https://doi.org/10.1016/j.bmcl.2015.09.049]en_US
dc.identifier.issn0960-894X
dc.identifier.issn1464-3405 (Online)
dc.identifier.urihttp://hdl.handle.net/10394/18349
dc.identifier.urihttps://www.sciencedirect.com/science/article/pii/S0960894X15300834
dc.identifier.urihttps://doi.org/10.1016/j.bmcl.2015.09.049
dc.description.abstractStudies have shown that natural and synthetic chalcones (1,3-diphenyl-2-propen-1-ones) possess monoamine oxidase (MAO) inhibition activities. Of particular importance to the present study is a report that a series of furanochalcones acts as MAO-B selective inhibitors. Since the effect of heterocyclic substitution, other than furan (and more recently thiophene, piperidine and quinoline) on the MAO inhibitory properties of the chalcone scaffold remains unexplored, the aim of this study was to synthesise and evaluate further heterocyclic chalcone analogues as inhibitors of the human MAOs. For this purpose, heterocyclic chalcone analogues that incorporate pyrrole, 5-methylthiophene, 5-chlorothiophene and 6-methoxypyridine substitution were examined. Seven of the nine synthesised compounds exhibited IC50 values <1 μM for the inhibition of MAO-B, with all compounds exhibiting higher affinities for MAO-B compared to the MAO-A isoform. The most potent MAO-B inhibitor (4h) displays an IC50 value of 0.067 μM while the most potent MAO-A inhibitor (4e) exhibits an IC50 value of 3.81 μM. It was further established that selected heterocyclic chalcones are reversible and competitive MAO inhibitors. 4h, however, may exhibit tight-binding to MAO-B, a property linked to its thiophene moiety. We conclude that high potency chalcones such as 4h represent suitable leads for the development of MAO-B inhibitors for the treatment of Parkinson’s disease and possibly other neurodegenerative disordersen_US
dc.description.sponsorshipMedical Research Council of South Africa and National Research Foundation of South Africa (Grant specific unique reference numbers (UID) 85642, 80647, 96180 and 76308)en_US
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.subjectMonoamine oxidase (MAO)en_US
dc.subjectChalconeen_US
dc.subjectInhibitionen_US
dc.subjectCompetitiveen_US
dc.subjectReversibleen_US
dc.titleMonoamine oxidase inhibitory activities of heterocyclic chalconesen_US
dc.typeArticleen_US
dc.contributor.researchID20284462 - Minders, Corné
dc.contributor.researchID10727388 - Petzer, Jacobus Petrus
dc.contributor.researchID12264954 - Petzer, Anél
dc.contributor.researchID10948724 - Lourens, Anna Catharina U.


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