Symmetrical alpha-bromoacryloylamido diaryldienone derivatives as a novel series of antiproliferative agents. Design, synthesis and biological evaluation.
In a continuing study of hybrid compounds containing the alpha-bromoacryloyl moiety as potential anticancer drugs, we synthesized a novel series of hybrids 4a-h, in which this moiety was linked to a 1,5-diaryl-1,4-pentadien-3-one system. Many of the conjugates prepared (4b, 4c, 4e and 4g) demonstrated pronounced, submicromolar antiproliferative activity against four cancer cell lines. Moreover, compound 4b induced apoptosis through the mitochondrial pathway and activated caspase-3 in a concentration-dependent manner.
Romagnoli
Romeo
R
Dipartimento di Scienze Farmaceutiche, Università di Ferrara, 44100 Ferrara, Italy. rmr@unife.it
Baraldi
Pier Giovanni
PG
Cruz-Lopez
Olga
O
Lopez Cara
Carlota
C
Carrion
Maria Dora
MD
Balzarini
Jan
J
Hamel
Ernest
E
Basso
Giuseppe
G
Bortolozzi
Roberta
R
Viola
Giampietro
G
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D047188:Chalcones / Q000737:chemistry*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D051379:Mice
D000970:Antineoplastic Agents; D047188:Chalcones; D053148:Caspase 3