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
Farida TripodiPaola Coccetti

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.

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Jul 21, 2012·Pharmaceutical Research·Yan LuDuane D Miller
Jan 7, 2014·European Journal of Medicinal Chemistry·Dmitry V TsyganovVictor V Semenov
Aug 28, 2014·Future Medicinal Chemistry·Ilana ZaksArie Gruzman
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Sep 9, 2016·European Journal of Medicinal Chemistry·Ramasatyaveni GeesalaAmitava Das
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Mar 10, 2020·Current Topics in Medicinal Chemistry·Xinfen Zhang, Yanshu Jia
Jun 9, 2021·Journal of Medicinal Chemistry·Wen ShuaiYuxi Wang
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Nov 5, 2014·Journal of Medicinal Chemistry·Niamh M O'BoyleMary J Meegan
Sep 2, 2021·Future Medicinal Chemistry·Siddappa A PatilAlejandro Bugarin

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