Through scaffold modification to 3,5-diaryl-4,5-dihydroisoxazoles: new potent and selective inhibitors of monoamine oxidase B |
| |
| Authors: | Rita Meleddu Simona Distinto Roberto Cirilli Stefano Alcaro Matilde Yanez Maria Luisa Sanna |
| |
| Affiliation: | 1. Department of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy;2. Dipartimento del Farmaco, Istituto Superiore di Sanità, Rome, Italy;3. Dipartimento di Scienze della Salute, Università Magna Gr?cia di Catanzaro, Catanzaro, Italy;4. Departamento de Farmacología and Instituto de Farmacia Industrial, Universidad de Santiago de Compostela, Campus Universitario Sur, Santiago de Compostela, Spain |
| |
| 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. |
| |
| Keywords: | 3,5-diaryl-dihydroisoxazoles MAO B selective inhibitors neuroprotective agents |
|
|
