Synthesis and pharmacological evaluation of coumarins as new scaffold on the Parkinson´s disease

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 8-bromo-6-methyl-3-phenylcoumarin derivatives without substituent and with different number of methoxy substituent in the 3-phenyl ring. The substituent in this new scaffold was introduced in the 3', 4' and/or 5' positions of the 3-phenyl ring of the coumarin moiety. The synthesized compounds 3-6 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 nanomolar range. Compounds 3 (11.05±0.81 nM), 4 (3.23±0.49 nM) and 5 (7.12±0.01 nM) show higher activity than selegiline (IC50 = 19.60 nM), and high MAO-B selectivity with 9,050- fold, 30,960-fold and 14,045-fold inhibition levels, with respect to the MAO-A isoform