Synthesis and biological evaluation of 1,4-diaryl-2-azetidinones as specific anticancer agents: Activation of adenosine monophosphate activated protein kinase and induction of apoptosis

Farida Tripodi, Roberto Pagliarin, Gabriele Fumagalli, Alessandra Bigi, Paola Fusi, Fulvia Orsini, Milo Frattini, Paola Coccetti

Research output: Contribution to journalArticle

Abstract

A series of novel 1,4-diaryl-2-azetidinones were synthesized and evaluated for antiproliferative activity, cell cycle effects, and apoptosis induction. Strong cytotoxicity was observed with the best compounds (±)-trans-20, (±)-trans-21, and enantiomers (+)-trans-20 and (+)-trans-21, which exhibited IC 50 values of 3-13 nM against duodenal adenocarcinoma cells. They induced inhibition of tubulin polymerization and subsequent G2/M arrest. This effect was accompanied by activation of AMP-activated protein kinase (AMPK), activation of caspase-3, and induction of apoptosis. Additionally, the most potent compounds displayed antiproliferative activity against different colon cancer cell lines, opening the route to a new class of potential therapeutic agents against colon cancer.

Original languageEnglish
Pages (from-to)2112-2124
Number of pages13
JournalJournal of Medicinal Chemistry
Volume55
Issue number5
DOIs
Publication statusPublished - Mar 8 2012

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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