Homoisoflavonoids: natural scaffolds with potent and selective monoamine oxidase-B inhibition properties.
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Desideri N, Bolasco A, Fioravanti R, Monaco LP, Orallo F, Yanez M, Ortuso F, Alcaro S
Homoisoflavonoids: natural scaffolds with potent and selective monoamine oxidase-B inhibition properties.
J Med Chem. 2011 Apr 14;54(7):2155-64. doi: 10.1021/jm1013709. Epub 2011 Mar 15.
- PubMed ID
- 21405131 [ View in PubMed]
- Abstract
A series of homoisoflavonoids [(E)-3-benzylidenechroman-4-ones 1a-w, 3-benzyl-4H-chromen-4-ones 2a-g, and 3-benzylchroman-4-ones 3a-e] have been synthesized and tested in vitro as inhibitors of human monoamine oxidase isoforms A and B (hMAO-A and hMAO-B). Most of the compounds were found to be potent and selective MAO-B inhibitors. In general, the (E)-3-benzylidenechroman-4-ones 1a-w showed activities in the nano- or micromolar range coupled with high selectivity against hMAO-B. The reduction of the exocyclic double bond results in compounds 3a-e selective against isoform B and active in the micromolar range. In contrast, the endocyclic migration of the double bond (compounds 2a-g) generally produces the loss of the inhibitory activity or a marked reduction in potency. (E)-3-(4-(Dimethylamino)benzylidene)chroman-4-one (1l) and (E)-5,7-dihydroxy-3-(4-hydroxybenzylidene)chroman-4-one (1h) were the most interesting compounds of the entire series of inhibitors, showing hMAO-B affinity better than the selective inhibitor selegiline. Molecular modeling studies have been carried out to explain the selectivity of the most active homoisoflavonoids 1h and 1l.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Clorgiline Amine oxidase [flavin-containing] A IC 50 (nM) 4.46 N/A N/A Details Iproniazid Amine oxidase [flavin-containing] B IC 50 (nM) 7540 N/A N/A Details Moclobemide Amine oxidase [flavin-containing] A IC 50 (nM) 361000 N/A N/A Details Selegiline Amine oxidase [flavin-containing] A IC 50 (nM) 67250 N/A N/A Details Selegiline Amine oxidase [flavin-containing] B IC 50 (nM) 19.6 N/A N/A Details