title: The synthesis and evaluation of sesamol and benzodioxane derivatives as inhibitors of monoamine oxidase.
abstract: In the present study, series of eight sesamol (1,3-benzodioxol-5-ol) and eight benzodioxane (2,3-dihydro-1,4-benzodioxine) derivatives were synthesised and evaluated as inhibitors of recombinant human monoamine oxidase (MAO) A and B. The sesamol and benzodioxane derivatives are structurally related to series of phthalide derivatives, which have previously been found to act as potent reversible MAO inhibitors. The results document that the benzodioxane derivatives, in particular, are potent MAO-B inhibitors with IC50 values ranging from 0.045 to 0.947 μM. IC50 values for the inhibition of MAO-B by the homologous series of sesamol derivatives ranged from 0.164 to 7.29 μM. All compounds evaluated are selective for the MAO-B isoform, with IC50 values for the inhibition of MAO-A ranging from 13.2 to >100 μM. It is further shown that for the most potent MAO-B inhibitor, 6-[(3-bromophenyl)methoxy]-2,3-dihydro-1,4-benzodioxine, inhibition is almost completely reversed by dialysis of enzyme-inhibitor mixtures. It may be concluded that benzodioxane derivatives are promising leads for the design of selective MAO-B inhibitors for the treatment of Parkinson's disease.
authors: Pharmaceutical Chemistry, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa; Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa.
authors: Idalet
authors: I
authors: Engelbrecht
authors: Pharmaceutical Chemistry, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa; Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa.
authors: Jacobus P
authors: JP
authors: Petzer
authors: Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa. Electronic address: 12264954@nwu.ac.za.
authors: Anél
authors: A
authors: Petzer
mesh_terms: D052117:Benzodioxoles / Q000737:chemistry* / Q000494:pharmacology*; D004146:Dioxanes / Q000737:chemistry* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015394:Molecular Structure; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010636:Phenols / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D052117:Benzodioxoles; D004146:Dioxanes; D008996:Monoamine Oxidase Inhibitors; D010636:Phenols; C025583:sesamol; D008995:Monoamine Oxidase
keywords: Benzodioxane; Inhibition; MAO; Monoamine oxidase; Selective; Sesamol