Synthesis and study of a series of 3-arylcoumarins as potent and selective monoamine oxidase B inhibitors.

Article Details

Citation

Matos MJ, Teran C, Perez-Castillo Y, Uriarte E, Santana L, Vina D

Synthesis and study of a series of 3-arylcoumarins as potent and selective monoamine oxidase B inhibitors.

J Med Chem. 2011 Oct 27;54(20):7127-37. doi: 10.1021/jm200716y. Epub 2011 Sep 29.

PubMed ID
21923181 [ View in PubMed
]
Abstract

New series of 6-substituted-3-arylcoumarins displaying several alkyl, hydroxyl, halogen, and alkoxy groups in the two benzene rings have been designed, synthesized, and evaluated in vitro as human monoamine oxidase A and B (hMAO-A and hMAO-B) inhibitors. Most of the studied compounds showed a high affinity and selectivity to the hMAO-B isoenzyme, with IC(50) values on nanomolar and picomolar range. Ten of the 22 described compounds displayed higher MAO-B inhibitory activity and selectivity than selegiline. Coumarin 7 is the most active compound of this series, being 64 times more active than selegiline and also showing the highest hMAO-B specificity. In addition, docking experiments were carried out on hMAO-A and h-MAO-B structures. This study provided new information about the enzyme-inhibitor interaction and the potential therapeutic application of this 3-arylcoumarin scaffold.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
IproniazidAmine oxidase [flavin-containing] BIC 50 (nM)7540N/AN/ADetails
SelegilineAmine oxidase [flavin-containing] AIC 50 (nM)67250N/AN/ADetails
SelegilineAmine oxidase [flavin-containing] BIC 50 (nM)19.6N/AN/ADetails