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

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