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 as well as enantiomers (+)-trans-20 and (+)-trans-21, which exhibited IC50 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.

Tripodi, F., Pagliarin, R., Fumagalli, G., Bigi, A., Fusi, P., Orsini, F., et al. (2012). 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. JOURNAL OF MEDICINAL CHEMISTRY, 55(5), 2112-2124 [10.1021/jm201344a].

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

TRIPODI, FARIDA;BIGI, ALESSANDRA;FUSI, PAOLA ALESSANDRA;COCCETTI, PAOLA
2012

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 as well as enantiomers (+)-trans-20 and (+)-trans-21, which exhibited IC50 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.
Articolo in rivista - Articolo scientifico
anticancer agents, azetidinones; AMPK; apoptosis
English
2012
55
5
2112
2124
none
Tripodi, F., Pagliarin, R., Fumagalli, G., Bigi, A., Fusi, P., Orsini, F., et al. (2012). 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. JOURNAL OF MEDICINAL CHEMISTRY, 55(5), 2112-2124 [10.1021/jm201344a].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/28595
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