Article: article from journal or magazin.
Inhibition of monoamine oxidases by functionalized coumarin derivatives: biological activities, QSARs, and 3D-QSARs.
Journal of Medicinal Chemistry
Publication types: In Vitro ; Journal Article
A large series of coumarin derivatives (71 compounds) were tested for their monoamine oxidase A and B (MAO-A and MAO-B) inhibitory activity. Most of the compounds acted preferentially on MAO-B with IC(50) values in the micromolar to low-nanomolar range; high inhibitory activities toward MAO-A were also measured for sulfonic acid esters. The most active compound was 7-[(3, 4-difluorobenzyl)oxy]-3,4-dimethylcoumarin, with an IC(50) value toward MAO-B of 1.14 nM. A QSAR study of 7-X-benzyloxy meta-substituted 3,4-dimethylcoumarin derivatives acting on MAO-B yielded good statistical results (q(2)() = 0.72, r(2)() = 0.86), revealing the importance of lipophilic interactions in modulating the inhibition and excluding any dependence on electronic properties. CoMFA was performed on two data sets of MAO-A and MAO-B inhibitors. The GOLPE procedure, with variable selection criteria, was applied to improve the predictivity of the models and to facilitate the graphical interpretation of results.
Animals, Bicyclo Compounds/chemical synthesis, Bicyclo Compounds/chemistry, Chromones/chemical synthesis, Chromones/chemistry, Coumarins/chemical synthesis, Coumarins/chemistry, Models, Molecular, Monoamine Oxidase/metabolism, Monoamine Oxidase Inhibitors/chemical synthesis, Monoamine Oxidase Inhibitors/chemistry, Quantitative Structure-Activity Relationship, Rats, Spectrophotometry, Ultraviolet
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