title: Interaction of indole derivatives with monoamine oxidase A and B. Studies on the structure-inhibitory activity relationship.
abstract: Indole and isatin (2,3-dioxindole) analogues were studied as inhibitors of MAO-A and B. They exhibited reversible and competitive MAO inhibition. Three dimensional structures of the compounds tested were constructed and minimized using PC-based molecular graphic software. The QSAR analysis revealed the requirement of co-planar structure of substituents at C2 and C3 of indole ring for selective MAO-A inhibition, whilst type of bond was less essential. The presence of hydroxy group at C5 of isatin increased selectivity of MAO-A inhibition, however simultaneous insertion of substituents into both positions of indole ring (5-hydroxy-2-phenylindole) led to a decrease of MAO-A inhibition. The planar molecules demonstrating potent MAO-A inhibition have the average sizes 7 A in length and 6 A in width. The MAO B inhibition also depended on the sizes of planar molecules however distribution of electron density in the molecules was another precondition for the selective inhibition of the enzyme.
authors.affiliation: Institute of Biomedical Chemistry, Russian Academy of Medical Sciences.
authors.forename: A E
authors.initials: AE
authors.lastname: Medvedev
authors.forename: A S
authors.initials: AS
authors.lastname: Ivanov
authors.forename: N S
authors.initials: NS
authors.lastname: Kamyshanskaya
authors.forename: A Z
authors.initials: AZ
authors.lastname: Kirkel
authors.forename: T A
authors.initials: TA
authors.lastname: Moskvitina
authors.forename: V Z
authors.initials: VZ
authors.lastname: Gorkin
authors.forename: N Y
authors.initials: NY
authors.lastname: Li
authors.lastname: Marshakov VYu
mesh_terms: D000818:Animals; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D007510:Isatin / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D008928:Mitochondria / Q000201:enzymology*; D015394:Molecular Structure; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D007211:Indoles; D008996:Monoamine Oxidase Inhibitors; D007510:Isatin; D008995:Monoamine Oxidase