A series of spiro[isoindole-1,5-isoxazolidin]-3(2H)-ones has been synthesized by 1,3-dipolar cycloaddition of N-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.

Giofrè, S., Cirmi, S., Mancuso, R., Nicolò, F., Lanza, G., Legnani, L., et al. (2016). Synthesis of spiro[isoindole-1,5′-isoxazolidin]-3(2H)-ones as potential inhibitors of the MDM2-p53 interaction. BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY, 12, 2793-2807 [10.3762/bjoc.12.278].

Synthesis of spiro[isoindole-1,5′-isoxazolidin]-3(2H)-ones as potential inhibitors of the MDM2-p53 interaction

LEGNANI, LAURA;
2016

Abstract

A series of spiro[isoindole-1,5-isoxazolidin]-3(2H)-ones has been synthesized by 1,3-dipolar cycloaddition of N-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.
Articolo in rivista - Articolo scientifico
1,3-Dipolar cycloaddition; Antitumor agents; DFT studies; Docking studies; Spiro-compounds;
English
2793
2807
15
Giofrè, S., Cirmi, S., Mancuso, R., Nicolò, F., Lanza, G., Legnani, L., et al. (2016). Synthesis of spiro[isoindole-1,5′-isoxazolidin]-3(2H)-ones as potential inhibitors of the MDM2-p53 interaction. BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY, 12, 2793-2807 [10.3762/bjoc.12.278].
Giofrè, S; Cirmi, S; Mancuso, R; Nicolò, F; Lanza, G; Legnani, L; Campisi, A; Chiacchio, M; Navarra, M; Gabriele, B; Romeo, R
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/352011
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