Design, Synthesis and Pharmacological Evaluation of New Coumarin Derivatives as Monoamine Oxidase A and 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 design, synthesis and pharmacological evaluation of a new series of coumarin derivatives with 4-methyl or cycloalkene or benzene ring condensed in the 3,4 position. The substituents in this new scaffold were introduced in the 5, 7 and/or 8 positions of the coumarin moiety. The synthesized compounds 1-13 were evaluated as MAO A and B inhibitors using clorgyline and selegiline, respectively, as reference inhibitors, showing, most of them, activities in the nanomolar range. Compounds 6 (IC50 = 1.18 nM) and 10 (IC50 = 1.48 nM), show higher activity than selegiline (IC50 = 19.60 nM), and high MAO-B selectivity with 100-fold and 1600-fold inhibition levels, with respect to the MAO-A isoform