Design, synthesis, and biological evaluation of hybrid molecules containing alpha-methylene-gamma-butyrolactones and alpha-bromoacryloyl moieties.
The synthesis and biological activity of hybrids 8-18 prepared combining alpha-methylene-gamma-butyrolactones and alpha-bromoacryloylamides have been described and their structure-activity relationships discussed. All these heterobifunctional compounds demonstrate good antileukemic activity, significantly superior to that of both alkylating units alone. Using the human leukemia HL-60 cell line, selected compounds 10, 11, 13, and 17 were found to induce morphological changes and internucleosomal DNA fragmentation characteristic of apoptotic cell death.
Romagnoli
Romeo
R
Dipartimento di Scienze Farmaceutiche, Università di Ferrara, 44100 Ferrara, Italy.
Baraldi
Pier Giovanni
PG
Tabrizi
Mojgan Aghazadeh
MA
Bermejo
Jaime
J
Estévez
Francisco
F
Borgatti
Monica
M
Gambari
Roberto
R
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D000178:Acrylamides / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D017209:Apoptosis; D045744:Cell Line, Tumor; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D013329:Structure-Activity Relationship
D000178:Acrylamides; D000970:Antineoplastic Agents; D015107:4-Butyrolactone