Hydroxycoumarins as selective MAO-B inhibitors.

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Serra S, Ferino G, Matos MJ, Vazquez-Rodriguez S, Delogu G, Vina D, Cadoni E, Santana L, Uriarte E

Hydroxycoumarins as selective MAO-B inhibitors.

Bioorg Med Chem Lett. 2012 Jan 1;22(1):258-61. doi: 10.1016/j.bmcl.2011.11.020. Epub 2011 Nov 11.

PubMed ID
22137786 [ View in PubMed
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Abstract

A series of 3-aryl-4-hydroxycoumarin derivatives was synthesized with the aim to find out the structural features for the MAO inhibitory activity and selectivity. Methoxy and/or chloro substituents were introduced in the 3-phenyl ring, whereas the position 6 in the coumarin moiety was not substituted or substituted with a methyl group or a chloro atom due to their different electronic, steric and/or lipophilic properties. Most of the synthesized compounds presented MAO-B inhibitory activity. The presence of methoxy and chloro groups, respectively in the para and meta positions of the 3-phenyl ring, have an important influence on the inhibitory activity. Moreover, the presence of a chloro atom in the six position of the moiety (compound 7) improved the inhibitor activity as well as its selectivity against MAO-B compared with iproniazide, used as reference compound. Docking experiments were carried out to understand which are the most energetically preferred orientations adopted by compounds 5, 6 and 7 inside the MAO-B binding pocket.

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)68730N/AN/ADetails
SelegilineAmine oxidase [flavin-containing] BIC 50 (nM)17N/AN/ADetails