TY - JOUR
T1 - Synthesis and biological evaluation of 1,4-diaryl-2-azetidinones as specific anticancer agents
T2 - Activation of adenosine monophosphate activated protein kinase and induction of apoptosis
AU - Tripodi, Farida
AU - Pagliarin, Roberto
AU - Fumagalli, Gabriele
AU - Bigi, Alessandra
AU - Fusi, Paola
AU - Orsini, Fulvia
AU - Frattini, Milo
AU - Coccetti, Paola
PY - 2012/3/8
Y1 - 2012/3/8
N2 - 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.
AB - 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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U2 - 10.1021/jm201344a
DO - 10.1021/jm201344a
M3 - Article
C2 - 22329561
AN - SCOPUS:84858057079
VL - 55
SP - 2112
EP - 2124
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 5
ER -