title: Selective inhibitors and computer modelling of the active site of monoamine oxidase.
abstract: MAO inhibitors can be employed for computer modelling of the active site of MAO A and B. Competitive fully reversible MAO inhibitors with rigid structure and limited number of conformers are preferential compounds for these studies. Among various isatin analogues with nearllanar structure selective MAO B inhibitors fit to 3D box of 8.5x5.1x1.8 A, whereas 3D box of 14.2x5.6x1.8 A accommodates selective MAO A inhibitors. Validity of these data was tested using a series of pyrazinocarbazoles, analogues of short-acting antidepressant pirlindole. Rigid analogues exhibiting potent and selective inhibition of MAO A have 3D size limits of 13x7x4.4 A. Flexible analogues also demonstrated potent inhibition of MAO B and in contrast to rigid analogues their inhibitory activity did not show any dependence on 3D sizes. 3D-QSAR with CoMFA of isatin and pirlindole analogues of MAO A and B revealed differences in the models of MAO A and B.
authors.affiliation: Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, Moscow. medvedev@ibmh.nsk.su
authors.forename: A E
authors.initials: AE
authors.lastname: Medvedev
authors.forename: A S
authors.initials: AS
authors.lastname: Ivanov
authors.forename: A V
authors.initials: AV
authors.lastname: Veselovsky
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002227:Carbazoles / Q000737:chemistry; D003198:Computer Simulation; D007510:Isatin / Q000737:chemistry; D008099:Liver / Q000201:enzymology; D008956:Models, Chemical; D008969:Molecular Sequence Data; D008995:Monoamine Oxidase / Q000737:chemistry*; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry; D051381:Rats
chemical_list: D002227:Carbazoles; D008996:Monoamine Oxidase Inhibitors; D007510:Isatin; D008995:Monoamine Oxidase; C009830:pirlindole