title: Evaluation of Natural and Synthetic 1,4-naphthoquinones as Inhibitors of Monoamine Oxidase.
abstract: Previous reports have documented that 1,4-naphthoquinones act as inhibitors of the monoamine oxidase (MAO) enzymes. In particular, fractionation of the extracts of cured tobacco leafs has led to the characterization of 2,3,6-trimethyl-1,4-naphthoquinone, a non-selective MAO inhibitor. To derive structure-activity relationships for MAO inhibition by the 1,4-naphthoquinone class of compounds, this study investigates the human MAO inhibitory activities of fourteen structurally diverse 1,4-naphthoquinones of natural and synthetic origin. Of these, 5,8-dihydroxy-1,4-naphthoquinone was found to be the most potent inhibitor with an IC50 value of 0.860 μm for the inhibition of MAO-B. A related compound, shikonin, inhibits both the MAO-A and MAO-B isoforms with IC50 values of 1.50 and 1.01 μm, respectively. It is further shown that MAO-A and MAO-B inhibition by these compounds is reversible by dialysis. In this respect, kinetic analysis suggests that the modes of MAO inhibition are competitive. This study contributes to the discovery of novel MAO inhibitors, which may be useful in the treatment for disorders such as Parkinson's disease, depressive illness, congestive heart failure and cancer.
authors.affiliation: 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.forename: Samantha
authors.initials: S
authors.lastname: Mostert
authors.affiliation: Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom, 2520, South Africa.
authors.forename: Anél
authors.initials: A
authors.lastname: Petzer
authors.affiliation: 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.forename: Jacobus P
authors.initials: JP
authors.lastname: Petzer
mesh_terms: D007700:Kinetics; D062105:Molecular Docking Simulation; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009285:Naphthoquinones / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D008996:Monoamine Oxidase Inhibitors; D009285:Naphthoquinones; C035342:1,4-naphthoquinone
keywords: 1,4-naphthoquinone; competitive; dialysis; inhibition; monoamine oxidase; reversible