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

Rita Meleddu, Simona Distinto, Roberto Cirilli, Stefano Alcaro, Matilde Yanez, Maria Luisa Sanna, Angela Corona, Claudia Melis, Giulia Bianco, P. Mátyus, Filippo Cottiglia, Elias Maccioni

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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.

Original languageEnglish
Pages (from-to)264-270
Number of pages7
JournalJournal of Enzyme Inhibition and Medicinal Chemistry
Volume32
Issue number1
DOIs
Publication statusPublished - Dec 1 2017

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Keywords

  • 3,5-diaryl-dihydroisoxazoles
  • MAO B selective inhibitors
  • neuroprotective agents

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

Cite this

Meleddu, R., Distinto, S., Cirilli, R., Alcaro, S., Yanez, M., Sanna, M. L., Corona, A., Melis, C., Bianco, G., Mátyus, P., Cottiglia, F., & Maccioni, E. (2017). Through scaffold modification to 3,5-diaryl-4,5-dihydroisoxazoles: new potent and selective inhibitors of monoamine oxidase B. Journal of Enzyme Inhibition and Medicinal Chemistry, 32(1), 264-270. https://doi.org/10.1080/14756366.2016.1247061