title: Benzyloxynitrostyrene analogues - A novel class of selective and highly potent inhibitors of monoamine oxidase B.
abstract: This study examines a series of novel 3-benzyloxy-β-nitrostyrene analogues as a novel class of inhibitors of the monoamine oxidase (MAO) enzymes. MAO inhibitors are considered useful for the treatment of depression and Parkinson's disease, and have recently attracted attention as potential therapeutic agents for a range of disorders including Alzheimer's disease, prostate cancer and certain cardiomyopathies. This study shows that the 3-benzyloxy-β-nitrostyrene analogues are potent inhibitors of the MAO-B isoform with IC50values in the nanomolar range (39-565 nM). Significantly, effectiveness towards MAO-B inhibition seems to be governed by the introduction of a 4″-fluoro-substituent on the benzyloxy ring, with compound 2b exhibiting the highest degree of MAO-B inhibition potency (IC50= 0.039 μM) and selectivity (SI = 166) among the compounds investigated. Since some of the 3-benzyloxy-β-nitrostyrene analogues possess potencies that are comparable to that of the reversible inhibitor, safinamide (IC50= 0.080 μM), it may be concluded that this class may be promising leads for the development of reversible and selective MAO-B inhibitors, that may be useful for the management of Parkinson's disease.
authors.affiliation: Centre of Excellence for Pharmaceutical Sciences, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom, 2520, South Africa. Electronic address: dalenevanderwalt@gmail.com.
authors.forename: Mietha M
authors.initials: MM
authors.lastname: Van der Walt
authors.affiliation: Centre of Excellence for Pharmaceutical Sciences, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom, 2520, South Africa; Pharmaceutical Chemistry, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom, 2520, South Africa.
authors.forename: Gisella
authors.initials: G
authors.lastname: Terre'Blanche
authors.affiliation: Centre of Excellence for Pharmaceutical Sciences, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom, 2520, South Africa; Pharmaceutical Chemistry, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom, 2520, South Africa.
authors.forename: Jacobus P
authors.initials: JP
authors.lastname: Petzer
authors.affiliation: Centre of Excellence for Pharmaceutical Sciences, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom, 2520, South Africa; Pharmaceutical Chemistry, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom, 2520, South Africa.
authors.forename: Anél
authors.initials: A
authors.lastname: Petzer
mesh_terms: D006801:Humans; D007700:Kinetics; D008995:Monoamine Oxidase / Q000737:chemistry / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D010300:Parkinson Disease / Q000188:drug therapy; D013329:Structure-Activity Relationship; D013343:Styrenes / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D008996:Monoamine Oxidase Inhibitors; D013343:Styrenes; C011955:beta-nitrostyrene; D008995:Monoamine Oxidase
keywords: 3-benzyloxy-β-nitrostyrene analogues; Benzyloxynitrostyrene; Inhibition; MAO-B; Monoamine oxidase; Parkinson's disease; Slow reversible