Synthesis, modelling, and antimitotic properties of tricyclic systems characterised by a 2-(5-phenyl-1H-pyrrol-3-yl)-1,3,4-oxadiazole moiety

Gérard A. Pinna, Gabriele Murineddu, Caterina Murruzzu, Valentina Zuco, Franco Zunino, Graziella Cappelletti, Roberto Artali, Giorgio Cignarella, Lucrezia Solano, Stefania Villa

Research output: Contribution to journalArticle

Abstract

Interesting antitumour activity was observed in a series of tricyclic compounds characterised by the presence of a 2-(1H-pyrrol-3-yl)-1,3,4-oxadiazole moiety that is variously substituted. Their synthesis and antiproliferative activity toward a panel of human tumour cell lines is described. The two most interesting compounds were selected for further evaluation to elucidate their possible mechanism of action. Analysis of cell cycle, tubulin polymerisation, modulation of mitotic markers of the M phase, and apoptosis showed that antimitotic activity is the primary mechanism of the cytotoxic effects of these compounds. Experiments performed on isolated tubulin confirmed that the compounds act by inducing tubulin polymerisation, like taxanes. The binding model against tubulin was also examined by molecular modelling and docking. The results support the proposed binding model, which is able to explain the activity of the oxadiazole derivatives on the basis of their docking energy.

Original languageEnglish
Pages (from-to)998-1009
Number of pages12
JournalChemMedChem
Volume4
Issue number6
DOIs
Publication statusPublished - Jun 8 2009

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Keywords

  • Antitumor agents
  • Cytotoxicity
  • Molecular modeling
  • Oxadiazoles
  • Tubulin polymerisation

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry
  • Molecular Medicine

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