title: Novel sulfanylphthalimide analogues as highly potent inhibitors of monoamine oxidase B.
abstract: Monoamine oxidase (MAO) plays an essential role in the catabolism of neurotransmitter amines. The two isoforms of this enzyme, MAO-A and -B, are considered to be drug targets for the therapy of depression and neurodegenerative diseases, respectively. Based on a recent report that the phthalimide moiety may be a useful scaffold for the design of potent MAO-B inhibitors, the present study examines a series of 5-sulfanylphthalimide analogues as potential inhibitors of both human MAO isoforms. The results document that 5-sulfanylphthalimides are highly potent and selective MAO-B inhibitors with all of the examined compounds possessing IC(50) values in the nanomolar range. The most potent inhibitor, 5-(benzylsulfanyl)phthalimide, exhibits an IC(50) value of 0.0045 μM for the inhibition of MAO-B with a 427-fold selectivity for MAO-B compared to MAO-A. We conclude that 5-sulfanylphthalimides represent an interesting class of MAO-B inhibitors and may serve as lead compounds for the design of antiparkinsonian therapy.
authors.affiliation: Pharmaceutical Chemistry, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa.
authors.forename: Mietha M
authors.initials: MM
authors.lastname: Van der Walt
authors.forename: Gisella
authors.initials: G
authors.lastname: Terre'Blanche
authors.forename: Anél
authors.initials: A
authors.lastname: Petzer
authors.forename: Jacobus P
authors.initials: JP
authors.lastname: Petzer
mesh_terms: D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010797:Phthalimides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020033:Protein Isoforms
chemical_list: D008996:Monoamine Oxidase Inhibitors; D010797:Phthalimides; D020033:Protein Isoforms; D008995:Monoamine Oxidase