[1,2]Oxazolo[5,4-e]isoindoles as promising tubulin polymerization inhibitors

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

Research output: Contribution to journalArticle

Abstract

A series of [1,2]Oxazolo [5,4-e]isoindoles has been synthesized through a versatile and high yielding sequence. All the new structures showed in the 1HNMR spectra, the typical signal in the 8.34–8.47 ppm attributable to the H-3 of the [1,2]oxazole moiety. Among all derivatives, methoxy benzyl substituents at positions 3 and 4 or/and 5 were very effective in reducing the growth of different tumor cell lines, including diffuse malignant peritoneal mesothelioma (DMPM), an uncommon and rapidly malignancy poorly responsive to available therapeutic options. The most active compound 6j was found to impair tubulin polymerization, cause cell cycle arrest at G2/M phase and induce apoptosis in DMPM cells, making it as a new lead for the discovery of new potent antimitotic drugs.

Original languageEnglish
Pages (from-to)840-851
Number of pages12
JournalEuropean Journal of Medicinal Chemistry
Volume124
DOIs
Publication statusPublished - Nov 29 2016

Keywords

  • Antitubulin agents
  • Diffuse malignant peritoneal mesothelioma
  • [1,2]Oxazolo[5,4-e]isoindoles
  • α-hydroxyalkyl ketones

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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  • Cite this

    Spanò, V., Pennati, M., Parrino, B., Carbone, A., Montalbano, A., Lopergolo, A., Zuco, V., Cominetti, D., Diana, P., Cirrincione, G., Zaffaroni, N., & Barraja, P. (2016). [1,2]Oxazolo[5,4-e]isoindoles as promising tubulin polymerization inhibitors. European Journal of Medicinal Chemistry, 124, 840-851. https://doi.org/10.1016/j.ejmech.2016.09.013