title: 2-acetylphenol analogs as potent reversible monoamine oxidase inhibitors.
abstract: Based 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 disease.
authors.affiliation: Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom, South Africa.
authors.forename: Lesetja J
authors.initials: LJ
authors.lastname: Legoabe
authors.affiliation: Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom, South Africa.
authors.forename: Anél
authors.initials: A
authors.lastname: Petzer
authors.affiliation: Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom, South Africa ; Department of Pharmaceutical Chemistry, School of Pharmacy, North-West University, Potchefstroom, South Africa.
authors.forename: Jacobus P
authors.initials: JP
authors.lastname: Petzer
mesh_terms: D000098:Acetophenones / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D001667:Binding, Competitive; D002384:Catalysis; D015195:Drug Design; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D015394:Molecular Structure; D008995:Monoamine Oxidase / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D011994:Recombinant Proteins; D013329:Structure-Activity Relationship
chemical_list: D000098:Acetophenones; D008996:Monoamine Oxidase Inhibitors; D011994:Recombinant Proteins; D008995:Monoamine Oxidase; C579458:monoamine oxidase A, human
keywords: 2-acetylphenol; MAO; inhibition; monoamine oxidase; structure–activity relationship