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

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

Research output: Contribution to journalArticle

10 Citations (Scopus)

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
Publication statusPublished - 2016

Fingerprint

Isoindoles
Tubulin Modulators
Cells
Oxazoles
Antimitotic Agents
G2 Phase
Tubulin
Cell Cycle Checkpoints
Tumor Cell Line
Polymerization
Cell Division
Tumors
Apoptosis
Derivatives
Growth
Neoplasms
Malignant Mesothelioma
Therapeutics

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

[1,2]Oxazolo[5,4-e]isoindoles as promising tubulin polymerization inhibitors. / Spano', Virginia; Montalbano, Alessandra; Barraja, Paola; Parrino, Barbara; Diana, Patrizia; Carbone, Anna; Cirrincione, Girolamo; Lopergolo, Alessia; Cominetti, Denis; Pennati, Marzia; Zuco, Valentina; Zaffaroni, Nadia.

In: European Journal of Medicinal Chemistry, Vol. 124, 2016, p. 840-851.

Research output: Contribution to journalArticle

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AU - Montalbano, Alessandra

AU - Barraja, Paola

AU - Parrino, Barbara

AU - Diana, Patrizia

AU - Carbone, Anna

AU - Cirrincione, Girolamo

AU - Lopergolo, Alessia

AU - Cominetti, Denis

AU - Pennati, Marzia

AU - Zuco, Valentina

AU - Zaffaroni, Nadia

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AB - 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.

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