MAO inhibitory activity modulation: 3-Phenylcoumarins versus 3-benzoylcoumarins

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Abstract

With the aim of finding the structural features for the human MAO inhibitory activity and selectivity, in the present communication we report the synthesis, pharmacological evaluation and a comparative study of a new series of 3-phenylcoumarins (compounds 14) and 3-benzoylcoumarins (compounds 58). A bromo atom and a methoxy/hydroxy substituent were introduced in these scaffolds, at six and eight positions of the coumarin moiety, respectively. The synthesized compounds 1–8 were evaluated as MAO-A and B inhibitors using R-(−)-deprenyl and iproniazide as reference compounds. The presence or absence of a carbonyl group between the coumarin and the phenyl substituent in 3 position remarks, respectively, the MAO-A or MAO-B inhibitory activity. Some of the new compounds showed MAO-B inhibitory activities in the low nanomolar range. Compound 2 (IC50 = 1.35 nM) showed higher inhibitory activity than the R-(−)-deprenyl (IC50 = 19.60 nM) and higher MAO-B selectivity, with more than 74,074-fold inhibition level, respecting to the MAO-A isoform.

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Acknowledgments

Thanks to the Spanish Ministry (PS09/00501) and to Xunta de Galicia (PGIDIT09CSA030203PR and 10PXIB203303PR). M.J.M. thanks FCT for a PhD grant (SFRH/BD/61262/2009). S.V.R. thanks to Ministerio de Educación y Ciencia for a PhD grant (AP2008-04263).

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