Synthesis of Spiro[isoindole-1,5'-isoxazolidin]-3(2)-ones As Potential Inhibitors of the MDM2-p53 Interaction

Overview

Journal Beilstein J Org Chem

Specialty Chemistry

Date 2017 Feb 2

PMID 28144352

Citations 4

Authors

Salvatore V Giofre

Santa Cirmi

Raffaella Mancuso

Francesco Nicolo

Giuseppe Lanza

Laura Legnani

Agata Campisi

Maria A Chiacchio

Michele Navarra

Bartolo Gabriele

Roberto Romeo

Affiliations

Soon will be listed here.

Abstract

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.

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