Synthesis and evaluation of 6-methyl-3-phenylcoumarins as potent and selective MAO-B inhibitors

• Type: Article in International Scientific Journal
• Date: 2009

Authors

Matos, MJ (Author) Other; Viña, D (Author) Other; Picciau, C (Author) Other; Orallo, F (Author) Other; Santana, L (Author) Other; Uriarte, E (Author) Other

Journal

Title: Bioorganic and Medicinal Chemistry Letters

Vol. 19

Pages: 5053-5055

ISSN: 0960-894X

Publisher: Elsevier

Indexing

Scopus - 92 Citations

Other information

Authenticus ID: P-00R-0MF

DOI: 10.1016/j.bmcl.2009.07.039

Abstract (EN): A series of 6-methyl-3-phenylcoumarins 3-6 were synthesized and evaluated as monoamine oxidase A and B (MAO-A and MAO-B) inhibitors. A comparative study between the three possible mono methoxy 3-phenyl derivatives and the p-hydroxy analogue is reported. The synthesis of these new resveratrol-coumarin hybrids was carried out by a Perkin reaction between the 5-methylsalicylaldehyde and the corresponding phenylacetic acids. The p-methoxy substituted compound 3 was hydrolyzed to 6 by a traditional reaction with hydriodic acid. The prepared compounds show high selectivity to the MAO-B isoenzyme, some of them with IC50 values in the low nanomolar range. Compound 4, with the methoxy group in meta position, is the most active of this series, with an IC50 against MAO-B of 0.80 nM, and is several times more potent and MAO-B selective than the R-(-)-deprenyl (reference compound).

Language: English

Type (Professor's evaluation): Scientific