title: Inhibition of monoamine oxidase by indole and benzofuran derivatives.
abstract: Monoamine oxidase (MAO) is an important drug target for the treatment of neurological disorders. A series of indole and benzofuran derivatives were synthesised and evaluated as inhibitors of the two MAO isoforms, MAO-A and MAO-B. In general, the derivatives were found to be selective MAO-B inhibitors with K(i) values in the nanoMolar (nM) to microMolar (microM) concentration range. The most potent MAO-B inhibitor, 3,4-dichloro-N-(2-methyl-1H-indol-5-yl)benzamide, exhibited a K(i) value of 0.03 microM and was 99 fold more selective for the B isoform. We conclude that these indole and benzofuran derivatives are promising reversible MAO-B inhibitors with a possible role in the treatment of neurodegenerative diseases such as Parkinson's disease (PD).
authors.affiliation: Pharmaceutical Chemistry, School of Pharmacy, North-West University, Private Bag X6001, Potchefstroom 2520, South Africa.
authors.forename: Louis H A
authors.initials: LH
authors.lastname: Prins
authors.forename: Jacobus P
authors.initials: JP
authors.lastname: Petzer
authors.forename: Sarel F
authors.initials: SF
authors.lastname: Malan
mesh_terms: D001572:Benzofurans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D010300:Parkinson Disease / Q000188:drug therapy; D013329:Structure-Activity Relationship
chemical_list: D001572:Benzofurans; D007211:Indoles; D008996:Monoamine Oxidase Inhibitors; D008995:Monoamine Oxidase