title: New halogenated 3-phenylcoumarins as potent and selective MAO-B inhibitors.
abstract: With the aim to find out the structural features for the MAO inhibitory activity and selectivity, in the present communication we report the synthesis and pharmacological evaluation of a new series of bromo-6-methyl-3-phenylcoumarin derivatives (with bromo atom in both different benzene rings of the skeleton) with and without different number of methoxy substituent at the 3-phenyl ring. The methoxy substituents were introduced, in this new scaffold, in the meta and/or para positions of the 3-phenyl ring. The synthesized compounds 3-7 were evaluated as MAO-A and B inhibitors using R-(-)-deprenyl (selegiline) and iproniazide as reference inhibitors, showing, most of them, MAO-B inhibitory activities in the low nanomolar range. Compounds 4 (IC(50)=11.05 nM), 5 (IC(50)=3.23 nM) and 6 (IC(50)=7.12 nM) show higher activity than selegiline (IC(50)=19.60 nM) and higher MAO-B selectivity, with more than 9050-fold, 30,960-fold and 14,045-fold inhibition levels, with respect to the MAO-A isoform.
authors.affiliation: Departamento de Química Orgánica, Facultad de Farmacia, Universidad de Santiago de Compostela, Santiago de Compostela, Spain. mariacmatos@gmail.com
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Matos
authors.forename: Dolores
authors.initials: D
authors.lastname: Viña
authors.forename: Patricia
authors.initials: P
authors.lastname: Janeiro
authors.forename: Fernanda
authors.initials: F
authors.lastname: Borges
authors.forename: Lourdes
authors.initials: L
authors.lastname: Santana
authors.forename: Eugenio
authors.initials: E
authors.lastname: Uriarte
mesh_terms: D003374:Coumarins / Q000737:chemistry / Q000494:pharmacology*; D006219:Halogens / Q000737:chemistry*; D008995:Monoamine Oxidase / Q000187:drug effects*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*
chemical_list: D003374:Coumarins; D006219:Halogens; D008996:Monoamine Oxidase Inhibitors; D008995:Monoamine Oxidase