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Scientific article
English

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

Published inJournal of medicinal chemistry, vol. 43, no. 25, p. 4747-4758
Publication date2000
Abstract

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.

Keywords
  • Animals
  • Bicyclo Compounds/*chemical synthesis/chemistry/pharmacology
  • Chromones/*chemical synthesis/chemistry/pharmacology
  • Coumarins/*chemical synthesis/chemistry/pharmacology
  • Models, Molecular
  • Monoamine Oxidase/*metabolism
  • Monoamine Oxidase Inhibitors/*chemical synthesis/chemistry/pharmacology
  • Quantitative Structure-Activity Relationship
  • Rats
  • Spectrophotometry, Ultraviolet
Affiliation Not a UNIGE publication
Citation (ISO format)
GNERRE, Carmela et al. Inhibition of monoamine oxidases by functionalized coumarin derivatives: biological activities, QSARs, and 3D-QSARs. In: Journal of medicinal chemistry, 2000, vol. 43, n° 25, p. 4747–4758. doi: 10.1021/jm001028o
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ISSN of the journal0022-2623
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