title: Selected chromone derivatives as inhibitors of monoamine oxidase.
abstract: A previous study has shown that a series of C6-benzyloxy substituted chromones exhibit high binding affinities for human monoamine oxidase (MAO) B. In an attempt to discover additional chromones with potent and selective MAO-B inhibitory potencies and to further examine the structure-activity relationships of MAO-B inhibition by chromones, the series was expanded with homologues containing polar functional groups on C3 of the chromone ring. The results demonstrate that 6-[(3-bromobenzyl)oxy]chromones containing acidic and aldehydic functional groups on C3 act as potent reversible MAO-B inhibitors with IC(50) values of 2.8 and 3.7 nM, respectively. Interestingly, a 2-hydroxy-2,3-dihydro-1-benzopyran-4-one derivative as well as open-ring 2-acetylphenol analogues of the chromones also were potent MAO-B inhibitors with IC(50) values ranging from 4 to 11 nM. Chromone derivatives containing the benzyloxy substituent on C5 of the chromone ring, however, exhibit MAO-B inhibition potencies that are several orders of magnitude weaker. High potency inhibitors of MAO-B may find application in the therapy of neurodegenerative disorders such as Parkinson's disease.
authors: Unit for Drug Research and Development, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa.
authors: Lesetja J
authors: LJ
authors: Legoabe
authors: Anél
authors: A
authors: Petzer
authors: Jacobus P
authors: JP
authors: Petzer
mesh_terms: D001578:Benzopyrans / Q000737:chemistry / Q000494:pharmacology; D002867:Chromones / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000201:enzymology; D010300:Parkinson Disease / Q000188:drug therapy / Q000201:enzymology; D020033:Protein Isoforms / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D001578:Benzopyrans; D002867:Chromones; D008996:Monoamine Oxidase Inhibitors; D020033:Protein Isoforms; D011994:Recombinant Proteins; C575677:benzopyran-4-one; D008995:Monoamine Oxidase