3,5-Diaryl-4,5-dihydroisoxazoles were synthesized and evaluated as monoamine oxidase (MAO) enzyme inhibitors and iron chelators. All compounds exhibited selective inhibitory activity towards the B isoform of MAO in the nanomolar concentration range. The best performing compound was preliminarily evaluated for its ability to bind iron II and III cations, indicating that neither iron II nor iron III is coordinated. The best compounds racemic mixtures were separated and single enantiomers inhibitory activity evaluated. Furthermore, none of the synthesised compounds exhibited activity towards MAO A. Overall, these data support our hypothesis that 3,5-diaryl-4,5-dihydroisoxazoles are promising scaffolds for the design of neuroprotective agents.

Through scaffold modification to 3,5-diaryl-4,5-dihydroisoxazoles: new potent and selective inhibitors of monoamine oxidase B

MELEDDU, RITA;DISTINTO, SIMONA;SANNA, MARIA LUISA;CORONA, ANGELA;MELIS, CLAUDIA;BIANCO, GIULIA;COTTIGLIA, FILIPPO;MACCIONI, ELIAS
2017-01-01

Abstract

3,5-Diaryl-4,5-dihydroisoxazoles were synthesized and evaluated as monoamine oxidase (MAO) enzyme inhibitors and iron chelators. All compounds exhibited selective inhibitory activity towards the B isoform of MAO in the nanomolar concentration range. The best performing compound was preliminarily evaluated for its ability to bind iron II and III cations, indicating that neither iron II nor iron III is coordinated. The best compounds racemic mixtures were separated and single enantiomers inhibitory activity evaluated. Furthermore, none of the synthesised compounds exhibited activity towards MAO A. Overall, these data support our hypothesis that 3,5-diaryl-4,5-dihydroisoxazoles are promising scaffolds for the design of neuroprotective agents.
2017
3,5-diaryl-dihydroisoxazoles; MAO B selective inhibitors; neuroprotective agents; Isoxazoles; Models, Molecular; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Structure-Activity Relationship; Pharmacology; Drug Discovery3003 Pharmaceutical Science
File in questo prodotto:
File Dimensione Formato  
Through scaffold modification to 3 5 diaryl 4 5 dihydroisoxazoles new potent and selective inhibitors of monoamine oxidase B.pdf

Solo gestori archivio

Descrizione: Articolo principale
Tipologia: versione editoriale (VoR)
Dimensione 1.55 MB
Formato Adobe PDF
1.55 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11584/212710
Citazioni
  • ???jsp.display-item.citation.pmc??? 5
  • Scopus 15
  • ???jsp.display-item.citation.isi??? 14
social impact