ChemMedChem
Department of Organic Chemistry, Faculty of Pharmacy, University of Santiago de Compostela, 15782 Santiago de Compostela (Spain).
Published: July 2014
The design, synthesis, pharmacological evaluation, and theoretical studies of a new series of halogenated 3-arylcoumarins were carried out with the aim of finding new structural and biological features. This series displays several alkyl, hydroxy, halogen, and/or alkoxy groups in both benzene rings of the 3-arylcoumarin scaffold. Most of the compounds studied show high affinity and selectivity for the human monoamine oxidase B (hMAO-B) isoenzyme, with IC50 values in the low nanomolar and picomolar range. Most of the evaluated compounds display higher MAO-B inhibitory activity and selectivity than selegiline (the reference compound). Coumarin 12 (3-(3-bromophenyl)-6-methylcoumarin) is the most active compound (IC50 =134 pM), being 140-fold more active than selegiline and showing the highest specificity for hMAO-B. To better understand the structure-activity relationships, docking experiments were carried out on human monoamine oxidase (A and B) structures. Finally, the prediction of passive blood-brain partitioning, based on in silico derived physicochemical descriptors, was performed.
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http://dx.doi.org/10.1002/cmdc.201300533 | DOI Listing |
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