Synthesis and Study of a Series of 3-Arylcoumarins as Potent and Selective Monoamine Oxidase B Inhibitors

New series of 6-substituted-3-arylcoumarins displaying several alkyl, hydroxyl, halogen, and alkoxy groups in the two benzene rings have been designed, synthesized, and evaluated in vitro as human monoamine oxidase A and B (hMAO-A and hMAO-B) inhibitors. Most of the studied compounds showed a high affinity and selectivity to the hMAO-B isoenzyme, with IC(50) values on nanomolar and picomolar range. Ten of the 22 described compounds displayed higher MAO-B inhibitory activity and selectivity than selegiline. Coumarin 7 is the most active compound of this series, being 64 times more active than selegiline and also showing the highest hMAO-B specificity. In addition, docking experiments were carried out on hMAO-A and h-MAO-B structures. This study provided new information about the enzyme-inhibitor interaction and the potential therapeutic application of this 3-arylcoumarin scaffold.