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

Autor: Salvatore V. Giofrè, Santa Cirmi, Raffaella Mancuso, Francesco Nicolò, Giuseppe Lanza, Laura Legnani, Agata Campisi, Maria A. Chiacchio, Michele Navarra, Bartolo Gabriele, Roberto Romeo
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Zdroj: Beilstein Journal of Organic Chemistry, Vol 12, Iss 1, Pp 2793-2807 (2016)
Druh dokumentu: article
ISSN: 1860-5397
DOI: 10.3762/bjoc.12.278
Popis: 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.
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