title: MAO inhibitory activity modulation: 3-Phenylcoumarins versus 3-benzoylcoumarins.
abstract: With the aim of finding the structural features for the human MAO inhibitory activity and selectivity, in the present communication we report the synthesis, pharmacological evaluation and a comparative study of a new series of 3-phenylcoumarins (compounds 1-4) and 3-benzoylcoumarins (compounds 5-8). A bromo atom and a methoxy/hydroxy substituent were introduced in these scaffolds, at six and eight positions of the coumarin moiety, respectively. The synthesized compounds 1-8 were evaluated as MAO-A and B inhibitors using R-(-)-deprenyl and iproniazide as reference compounds. The presence or absence of a carbonyl group between the coumarin and the phenyl substituent in 3 position remarks, respectively, the MAO-A or MAO-B inhibitory activity. Some of the new compounds showed MAO-B inhibitory activities in the low nanomolar range. Compound 2 (IC(50)=1.35nM) showed higher inhibitory activity than the R-(-)-deprenyl (IC(50)=19.60nM) and higher MAO-B selectivity, with more than 74,074-fold inhibition level, respecting to the MAO-A isoform.
authors.affiliation: Departamento de Química Orgánica, Facultad de Farmacia, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Matos
authors.forename: Saleta
authors.initials: S
authors.lastname: Vazquez-Rodriguez
authors.forename: Eugenio
authors.initials: E
authors.lastname: Uriarte
authors.forename: Lourdes
authors.initials: L
authors.lastname: Santana
authors.forename: Dolores
authors.initials: D
authors.lastname: Viña
mesh_terms: D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D007490:Iproniazid / Q000494:pharmacology; D008995:Monoamine Oxidase / Q000737:chemistry* / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D012642:Selegiline / Q000494:pharmacology
chemical_list: C561924:6-bromo-8-methoxy-3-(4'-methoxyphenyl)coumarin; D003374:Coumarins; D008996:Monoamine Oxidase Inhibitors; D012642:Selegiline; C030123:coumarin; D007490:Iproniazid; D008995:Monoamine Oxidase