title: Synthesis of spiro[isoindole-1,5'-isoxazolidin]-3(2H)-ones as potential inhibitors of the MDM2-p53 interaction.
abstract: A series of spiro[isoindole-1,5-isoxazolidin]-3(2H)-ones has been synthesized by 1,3-dipolar cycloaddition ofN-benzylnitrone with isoindolin-3-methylene-1-ones. The regio- and stereoselectivity of the process have been rationalized by computational methods. The obtained compounds show cytotoxic properties and antiproliferative activity in the range of 9-22 μM. Biological tests suggest that the antitumor activity could be linked to the inhibition of the protein-protein p53-MDM2 interaction. Docking measurements support the biological data.
authors.affiliation: Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche e Ambientali, Via S.S. Annunziata, 98168 Messina, Italy.
authors.forename: Salvatore V
authors.initials: SV
authors.lastname: Giofrè
authors.affiliation: Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche e Ambientali, Via S.S. Annunziata, 98168 Messina, Italy.
authors.forename: Santa
authors.initials: S
authors.lastname: Cirmi
authors.affiliation: Dipartimento di Chimica e Tecnologie Chimiche, Università della Calabria, Via P. Bucci, 12/C, 87036 Arcavacata di Rende (CS), Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Mancuso
authors.affiliation: Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche e Ambientali, Università di Messina, Viale F. Stagno d'Alcontres 31, 98166 Messina, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Nicolò
authors.affiliation: Dipartimento di Scienze del Farmaco, Università di Catania, Viale A. Doria, 95100 Catania, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lanza
authors.affiliation: Dipartimento di Chimica, Università di Pavia, Via Taramelli 12, 27100 Pavia, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Legnani
authors.affiliation: Dipartimento di Scienze del Farmaco, Università di Catania, Viale A. Doria, 95100 Catania, Italy.
authors.forename: Agata
authors.initials: A
authors.lastname: Campisi
authors.affiliation: Dipartimento di Scienze del Farmaco, Università di Catania, Viale A. Doria, 95100 Catania, Italy; Dipartimento di Chimica, Università di Pavia, Via Taramelli 12, 27100 Pavia, Italy.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Chiacchio
authors.affiliation: Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche e Ambientali, Via S.S. Annunziata, 98168 Messina, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Navarra
authors.affiliation: Dipartimento di Chimica e Tecnologie Chimiche, Università della Calabria, Via P. Bucci, 12/C, 87036 Arcavacata di Rende (CS), Italy.
authors.forename: Bartolo
authors.initials: B
authors.lastname: Gabriele
authors.affiliation: Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche e Ambientali, Via S.S. Annunziata, 98168 Messina, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Romeo
keywords: 1,3-dipolar cycloaddition; DFT studies; antitumor agents; docking studies; spiro-compounds