Back
Inhibition of monoamine oxidases by functionalized coumarin derivatives: biological activities, QSARs, and 3D-QSARs.
Journal article

Inhibition of monoamine oxidases by functionalized coumarin derivatives: biological activities, QSARs, and 3D-QSARs.

Show more…
  • 2000-12-22
Published in:
  • Journal of medicinal chemistry. - 2000
Animals
Bridged Bicyclo Compounds
Chromones
Coumarins
In Vitro Techniques
Models, Molecular
Monoamine Oxidase
Monoamine Oxidase Inhibitors
Quantitative Structure-Activity Relationship
Rats
Spectrophotometry, Ultraviolet
English 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.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/98657
Statistics
Document views: 35 File downloads: