Chromone, a privileged scaffold for the development of monoamine oxidase inhibitors.

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Gaspar A, Silva T, Yanez M, Vina D, Orallo F, Ortuso F, Uriarte E, Alcaro S, Borges F

Chromone, a privileged scaffold for the development of monoamine oxidase inhibitors.

J Med Chem. 2011 Jul 28;54(14):5165-73. doi: 10.1021/jm2004267. Epub 2011 Jul 1.

PubMed ID
21696156 [ View in PubMed
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Abstract

Two series of novel chromone derivatives were synthesized and investigated for their ability to inhibit the activity of monoamine oxidase. The SAR data indicate that chromone derivatives with substituents in position 3 of gamma-pyrone nucleus act preferably as MAO-B inhibitors, with IC(50) values in the nanomolar to micromolar range. Almost all chromone 3-carboxamides display selectivity toward MAO-B. Identical substitutions on position 2 of gamma-pyrone nucleus result in complete loss of activity in both isoforms (chromones 2-12 except 3 and 5). Notably, chromone (19) exhibits an MAO-B IC(50) of 63 nM, greater than 1000-fold selectivity over MAO-A, and behaves as a quasi-reversible inhibitor. Docking experiments onto the MAO binding of the most active compound highlight different interaction patterns among the isoforms A and B. The differential analysis of the solvation effects among the chromone isomers gave additional insight about the superior outline of the 3-substituted chromone derivatives.

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