Selective inhibitors and computer modelling of the active site of monoamine oxidase
Medvedev, A.E.; Ivanov, A.S.; Veselovsky, A.V.
Neurobiology 8(2): 201-214
2000
ISSN/ISBN: 1216-8068 PMID: 11061215 Document Number: 523012
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 ANG, whereas 3D box of 14.2X5.6X1.8 ANG 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 ANG. 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.