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

Article Details

Citation

Matos MJ, Vina D, Janeiro P, Borges F, Santana L, Uriarte E

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

Bioorg Med Chem Lett. 2010 Sep 1;20(17):5157-60. doi: 10.1016/j.bmcl.2010.07.013. Epub 2010 Jul 8.

PubMed ID
20659799 [ View in PubMed
]
Abstract

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.

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)19600N/AN/ADetails