2. Academic Validation
  3. [1,2]Oxazolo[5,4-e]isoindoles as promising tubulin polymerization inhibitors

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

  • Eur J Med Chem. 2016 Nov 29:124:840-851. doi: 10.1016/j.ejmech.2016.09.013.
Virginia Spanò 1,  Marzia Pennati 2,  Barbara Parrino 1,  Anna Carbone 1,  Alessandra Montalbano 1,  Alessia Lopergolo 2,  Valentina Zuco 2,  Denis Cominetti 2,  Patrizia Diana 1,  Girolamo Cirrincione 1,  Nadia Zaffaroni 2,  Paola Barraja 3
Affiliations

Affiliations

  • 1 Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Università di Palermo, 90123 Palermo, Italy.
  • 2 Molecular Pharmacology Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milano, Italy.
  • 3 Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Università di Palermo, 90123 Palermo, Italy. Electronic address: paola.barraja@unipa.it.
PMID: 27643641 DOI: 10.1016/j.ejmech.2016.09.013
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.

Keywords

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

Figures