Chalcones: a valid scaffold for monoamine oxidases inhibitors.

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Chimenti F, Fioravanti R, Bolasco A, Chimenti P, Secci D, Rossi F, Yanez M, Orallo F, Ortuso F, Alcaro S

Chalcones: a valid scaffold for monoamine oxidases inhibitors.

J Med Chem. 2009 May 14;52(9):2818-24. doi: 10.1021/jm801590u.

PubMed ID
19378991 [ View in PubMed
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Abstract

A large series of substituted chalcones have been synthesized and tested in vitro for their ability to inhibit human monoamine oxidases A and B (hMAO-A and hMAO-B). While all the compounds showed hMAO-B selective activity in the micro- and nanomolar ranges, the best results were obtained in the presence of chlorine and hydroxyl or methoxyl substituents. To better understand the enzyme-inhibitor interaction and to explain the selectivity of the most active compounds toward hMAO-B, molecular modeling studies were carried out on new, high resolution, hMAO-B crystallographic structures. For the only compound that also showed activity against hMAO-A as well as low selectivity, the molecular modeling study was also performed on the hMAO-A crystallographic structure. The docking technique provided new insight on the inhibition mechanism and the rational drug design of more potent/selective hMAO inhibitors based on the chalcone scaffold.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
ClorgilineAmine oxidase [flavin-containing] AIC 50 (nM)4.57.437Details
MoclobemideAmine oxidase [flavin-containing] AIC 50 (nM)3613807.437Details
SelegilineAmine oxidase [flavin-containing] AIC 50 (nM)672507.437Details