Research into the anti-tumor properties of chalcones has received significant attention over the last few years. Two novel large series of .alpha.-bromoacryloylamidochalcones contg. a pair of Michael acceptors in their structures, corresponding to the .alpha.-bromoacryloyl moiety and the .alpha.,.beta.-unsatd. ketone system of the chalcone framework, were synthesized and evaluated for antiproliferative activity against five cancer cell lines. Such hybrid derivs. demonstrated significantly increased anti-tumor activity compared with the corresponding amino chalcones. The most promising lead mols. were 4-BrC(:CH2)CONHC6H4CH:CHCOR[ R = C6H4OEt-4 (I), 2-thienyl] and 4-BrC(:CH2)CONHC6H4COCH:CHC6H2(OMe)3-2,3,4, which had the highest activity toward the five cell lines. Flow cytometry with K562 cells showed that the most active compds. resulted in a large proportion of the cells entering in the apoptotic sub-G0-G1 peak. Moreover, I induced apoptosis through the mitochondrial pathway and activated caspase-3.
Hybrid alpha-bromoacryloylamido chalcones. Design, synthesis and biological evaluation
ROMAGNOLI, Romeo;BARALDI, Pier Giovanni;CANELLA, Alessandro;GAMBARI, Roberto;
2009
Abstract
Research into the anti-tumor properties of chalcones has received significant attention over the last few years. Two novel large series of .alpha.-bromoacryloylamidochalcones contg. a pair of Michael acceptors in their structures, corresponding to the .alpha.-bromoacryloyl moiety and the .alpha.,.beta.-unsatd. ketone system of the chalcone framework, were synthesized and evaluated for antiproliferative activity against five cancer cell lines. Such hybrid derivs. demonstrated significantly increased anti-tumor activity compared with the corresponding amino chalcones. The most promising lead mols. were 4-BrC(:CH2)CONHC6H4CH:CHCOR[ R = C6H4OEt-4 (I), 2-thienyl] and 4-BrC(:CH2)CONHC6H4COCH:CHC6H2(OMe)3-2,3,4, which had the highest activity toward the five cell lines. Flow cytometry with K562 cells showed that the most active compds. resulted in a large proportion of the cells entering in the apoptotic sub-G0-G1 peak. Moreover, I induced apoptosis through the mitochondrial pathway and activated caspase-3.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
