Preclinical Activity of New [1,2]Oxazolo[5,4-e]isoindole Derivatives in Diffuse Malignant Peritoneal Mesothelioma

Virginia Spanò, Marzia Pennati, Barbara Parrino, Anna Carbone, Alessandra Montalbano, Vincenzo Cilibrasi, Valentina Zuco, Alessia Lopergolo, Denis Cominetti, Patrizia Diana, Girolamo Cirrincione, Paola Barraja, Nadia Zaffaroni

Research output: Contribution to journalArticlepeer-review


A series of 22 derivatives of the [1,2]oxazolo[5,4-e]isoindole system were synthesized through an efficient and versatile procedure that involves the annelation of the [1,2]oxazole moiety to the isoindole ring, producing derivatives with a wide substitution pattern. The structure-activity relationship indicates that the N-4-methoxybenzyl group appears crucial for potent activity. In addition, the presence of a 6-phenyl moiety is important and the best activity is reached with a 3,4,5-trimethoxy substituent. The most active compound, bearing both the structural features, was able to inhibit tumor cell proliferation at nanomolar concentrations when tested against the full NCI human tumor cell line panel. Interestingly, this compound was effective in reducing in vitro and in vivo cell growth, impairing cell cycle progression and inducing apoptosis, as a consequence of the inhibition of tubulin polymerization, in experimental models of diffuse malignant peritoneal mesothelioma (DMPM), a rapidly lethal disease, poorly responsive to conventional therapeutic strategies.

Original languageEnglish
Pages (from-to)7223-7238
Number of pages16
JournalJournal of Medicinal Chemistry
Issue number15
Publication statusPublished - Aug 11 2016

ASJC Scopus subject areas

  • Medicine(all)
  • Molecular Medicine
  • Drug Discovery

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