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

Chalcones: a valid scaffold for monoamine oxidases inhibitors.

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

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Dipartimento di Chimica e Tecnologie del Farmaco, Università degli Studi di Roma La Sapienza, P. le A. Moro 5, 00185 Roma, Italy.

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.

PMID:: 19378991; [PubMed - indexed for MEDLINE]

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