Legoabe, Lesetja J.Petzer, AnélPetzer, Jacobus P.2016-08-192016-08-192015Legoabe, L.J. et al. 2015. 2-Acetylphenol analogs as potent reversible monoamine oxidase inhibitors. Drug design, development and therapy, 9:3635-3644. [https://doi.org/10.2147/DDDT.S86225l]1177-8881http://hdl.handle.net/10394/18330https://www.dovepress.com/2-acetylphenol-analogs-as-potent-reversible-monoamine-oxidase-inhibito-peer-reviewed-article-DDDThttps://doi.org/10.2147/DDDT.S86225Based on a previous report that substituted 2-acetylphenols may be promising leads for the design of novel monoamine oxidase (MAO) inhibitors, a series of C5-substituted 2-acetylphenol analogs (15) and related compounds (two) were synthesized and evaluated as inhibitors of human MAO-A and MAO-B. Generally, the study compounds exhibited inhibitory activities against both MAO-A and MAO-B, with selectivity for the B isoform. Among the compounds evaluated, seven compounds exhibited IC50 values ,0.01 μM for MAO-B inhibition, with the most selective compound being 17,000-fold selective for MAO-B over the MAO-A isoform. Analyses of the structure–activity relationships for MAO inhibition show that substitution on the C5 position of the 2-acetylphenol moiety is a requirement for MAO-B inhibition, and the benzyloxy substituent is particularly favorable in this regard. This study concludes that C5-substituted 2-acetylphenol analogs are potent and selective MAO-B inhibitors, appropriate for the design of therapies for neurodegenerative disorders such as Parkinson’s diseaseenMAOMonoamine oxidaseInhibition2-AcetylphenolStructure-activity relationshipArticle