title: Inhibition of monoamine oxidase by pirlindole analogues: 3D-QSAR analysis.
abstract: A series of pirlindole analogues were tested as inhibitors of monoamine oxidase A and B. Although we did not find strict dependence between 3D-size of molecules and their inhibitory potency, rigid analogues exhibited potent and selective inhibition of MAO-A. They have 3D size limits of 13 angstroms (length) x 7 angstroms (height) x 4.4 angstroms (widths). Besides MAO-A inhibition flexible analogues also demonstrated potent inhibition of MAO-B. Five compounds were studied as inhibitors of purified human liver MAO-A. Their inhibitory potencies coincided with those obtained using rat liver mitochondrial MAO-A. Each compound induced changes in the spectrum of MAO-A but these did not correlate with the flexibility of the derivative. It is also possible that the oxygen bridge introduced with the flexibility might influence spectral patterns.
authors.affiliation: Institute of Biomedical Chemistry, Moscow, Russia.
authors.forename: A E
authors.initials: AE
authors.lastname: Medvedev
authors.forename: R R
authors.initials: RR
authors.lastname: Ramsay
authors.forename: A S
authors.initials: AS
authors.lastname: Ivanov
authors.forename: A V
authors.initials: AV
authors.lastname: Veselovsky
authors.forename: V I
authors.initials: VI
authors.lastname: Shvedov
authors.forename: O V
authors.initials: OV
authors.lastname: Tikhonova
authors.forename: A P
authors.initials: AP
authors.lastname: Barradas
authors.forename: C K
authors.initials: CK
authors.lastname: Davidson
authors.forename: T A
authors.initials: TA
authors.lastname: Moskvitina
authors.forename: O A
authors.initials: OA
authors.lastname: Fedotova
authors.forename: L N
authors.initials: LN
authors.lastname: Axenova
mesh_terms: D000818:Animals; D002227:Carbazoles / Q000737:chemistry / Q000494:pharmacology*; D003198:Computer Simulation; D006801:Humans; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology; D008958:Models, Molecular; D008995:Monoamine Oxidase / Q000187:drug effects* / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D010920:Placenta / Q000187:drug effects / Q000201:enzymology; D051381:Rats
chemical_list: D002227:Carbazoles; D008996:Monoamine Oxidase Inhibitors; C082644:tetrindole; D008995:Monoamine Oxidase; C009830:pirlindole