New halogenated 3-phenylcoumarins as potent and selective MAO-B inhibitors

• Type: Article in International Scientific Journal
• Date: 2010

Authors

Joao Matos, MJ (Author) Other; vina, dolores (Author) Other; janeiro, patricia (Author) Other; borges, fernanda (Author) FCUP; santana, lourdes (Author) Other; uriarte, eugenio (Author) Other

Journal

Title: Bioorganic and Medicinal Chemistry Letters

Vol. 20

Pages: 5157-5160

ISSN: 0960-894X

Publisher: Elsevier

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ISI Web of Knowledge - 80 Citations

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Other information

Authenticus ID: P-003-34Q

DOI: 10.1016/j.bmcl.2010.07.013

Abstract (EN): With the aim to find out the structural features for the MAO inhibitory activity and selectivity, in the present communication we report the synthesis and pharmacological evaluation of a new series of bromo-6-methyl-3-phenylcoumarin derivatives (with bromo atom in both different benzene rings of the skeleton) with and without different number of methoxy substituent at the 3-phenyl ring. The methoxy substituents were introduced, in this new scaffold, in the meta and/or para positions of the 3-phenyl ring. The synthesized compounds 3-7 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 low nanomolar range. Compounds 4 (IC(50) = 11.05 nM), 5 (IC(50) = 3.23 nM) and 6 (IC(50) = 7.12 nM) show higher activity than selegiline (IC(50) = 19.60 nM) and higher MAO-B selectivity, with more than 9050-fold, 30,960-fold and 14,045-fold inhibition levels, with respect to the MAO-A isoform. (C) 2010 Elsevier Ltd. All rights reserved.

Language: English

Type (Professor's evaluation): Scientific