Novel (coumarin-3-yl)carbamates as selective MAO-B inhibitors: Synthesis, in vitro and in vivo assays, theoretical evaluation of ADME properties and docking study

Abstract A series of (coumarin-3-yl)carbamates was synthesized and evaluated in vitro as monoamine oxidase (MAO-A and MAO-B) inhibitors. Most of the new compounds selectively inhibited MAO-B isoenzyme with IC 50 values in the micro or nanoMolar ranges. Since these compounds must achieve the brain cells, theoretical evaluation of ADME properties were also carried out. Compound 8 (benzyl(coumarin-3-yl)carbamate), which presented the most interesting in vitro MAO-B inhibitory profile ( IC 50 against MAO-B = 45 nM), was subjected to further studies. This in vitro MAO-B inhibitory activity is comparable with that of the selegiline, the reference compound ( IC 50 against MAO-B = 20 nM). Taking into account the in vitro results of compound 8 , in vivo assays and docking calculations were also carried out for this derivative.