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2-acetylphenol analogs as potent reversible monoamine oxidase inhibitors.
Drug Des Devel Ther. 2015; 9:3635-44.DD

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.

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Authors+Show Affiliations

Legoabe LJ
Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom, South Africa.
Petzer A
Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom, South Africa.
Petzer JP
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.

MeSH

AcetophenonesBinding, CompetitiveCatalysisDrug DesignHumansKineticsModels, BiologicalMolecular StructureMonoamine OxidaseMonoamine Oxidase InhibitorsProtein BindingRecombinant ProteinsStructure-Activity Relationship

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26203229

Citation

Legoabe, Lesetja J., et al. "2-acetylphenol Analogs as Potent Reversible Monoamine Oxidase Inhibitors." Drug Design, Development and Therapy, vol. 9, 2015, pp. 3635-44.
Legoabe LJ, Petzer A, Petzer JP. 2-acetylphenol analogs as potent reversible monoamine oxidase inhibitors. Drug Des Devel Ther. 2015;9:3635-44.
Legoabe, L. J., Petzer, A., & Petzer, J. P. (2015). 2-acetylphenol analogs as potent reversible monoamine oxidase inhibitors. Drug Design, Development and Therapy, 9, 3635-44. https://doi.org/10.2147/DDDT.S86225
Legoabe LJ, Petzer A, Petzer JP. 2-acetylphenol Analogs as Potent Reversible Monoamine Oxidase Inhibitors. Drug Des Devel Ther. 2015;9:3635-44. PubMed PMID: 26203229.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 2-acetylphenol analogs as potent reversible monoamine oxidase inhibitors. AU - Legoabe,Lesetja J, AU - Petzer,Anél, AU - Petzer,Jacobus P, Y1 - 2015/07/15/ PY - 2015/7/24/entrez PY - 2015/7/24/pubmed PY - 2016/4/8/medline KW - 2-acetylphenol KW - MAO KW - inhibition KW - monoamine oxidase KW - structure–activity relationship SP - 3635 EP - 44 JF - Drug design, development and therapy JO - Drug Des Devel Ther VL - 9 N2 - 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. SN - 1177-8881 UR - https://www.unboundmedicine.com/medline/citation/26203229/2_acetylphenol_analogs_as_potent_reversible_monoamine_oxidase_inhibitors_ DB - PRIME DP - Unbound Medicine ER -