Hybrid alpha-bromoacryloylamido chalcones. Design, synthesis and biological evaluation.
Research into the anti-tumor properties of chalcones has received significant attention over the last few years Two novel large series of alpha-bromoacryloylamido chalcones 1a-m and 2a-k containing a pair of Michael acceptors in their structures, corresponding to the alpha-bromoacryloyl moiety and the alpha,beta-unsaturated ketone system of the chalcone framework, were synthesized and evaluated for antiproliferative activity against five cancer cell lines. Such hybrid derivatives demonstrated significantly increased anti-tumor activity compared with the corresponding amino chalcones. The most promising lead molecules were 1k, 1m and 2j, which had the highest activity toward the five cell lines. Flow cytometry with K562 cells showed that the most active compounds resulted in a large proportion of the cells entering in the apoptotic sub-G0-G1 peak. Moreover, compound 1k induced apoptosis through the mitochondrial pathway and activated caspase-3.
Romagnoli
Romeo
R
Dipartimento di Scienze Farmaceutiche, Università di Ferrara, 44100 Ferrara, Italy. rmr@unife.it
Baraldi
Pier Giovanni
PG
Carrion
Maria Dora
MD
Cruz-Lopez
Olga
O
Cara
Carlota Lopez
CL
Balzarini
Jan
J
Hamel
Ernest
E
Canella
Alessandro
A
Fabbri
Enrica
E
Gambari
Roberto
R
Basso
Giuseppe
G
Viola
Giampietro
G
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle; D045744:Cell Line, Tumor; D047188:Chalcones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D020014:K562 Cells; D051379:Mice; D008928:Mitochondria / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
D000970:Antineoplastic Agents; D047188:Chalcones; D017382:Reactive Oxygen Species; D053148:Caspase 3