Chalcones: a valid scaffold for monoamine oxidases inhibitors.
Article Details
- CitationCopy to clipboard
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]
- 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
Drug Target Property Measurement pH Temperature (°C) Clorgiline Amine oxidase [flavin-containing] A IC 50 (nM) 4.5 7.4 37 Details Moclobemide Amine oxidase [flavin-containing] A IC 50 (nM) 361380 7.4 37 Details Selegiline Amine oxidase [flavin-containing] A IC 50 (nM) 67250 7.4 37 Details