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J Med Chem. 2011 Apr 14;54(7):2155-64. doi: 10.1021/jm1013709. Epub 2011 Mar 15.

Homoisoflavonoids: natural scaffolds with potent and selective monoamine oxidase-B inhibition properties.

Author information

1
Dipartimento di Chimica e Tecnologie del Farmaco, Università La Sapienza di Roma, P.le Aldo Moro, 5, 00185 Rome, Italy. nicoletta.desideri@uniroma1.it

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.

PMID:
21405131
DOI:
10.1021/jm1013709
[Indexed for MEDLINE]

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