title: Design, synthesis, and biological evaluation of hybrid molecules containing alpha-methylene-gamma-butyrolactones and alpha-bromoacryloyl moieties.
abstract: 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.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Ferrara, 44100 Ferrara, Italy.
authors.forename: Romeo
authors.initials: R
authors.lastname: Romagnoli
authors.forename: Pier Giovanni
authors.initials: PG
authors.lastname: Baraldi
authors.forename: Mojgan Aghazadeh
authors.initials: MA
authors.lastname: Tabrizi
authors.forename: Jaime
authors.initials: J
authors.lastname: Bermejo
authors.forename: Francisco
authors.initials: F
authors.lastname: Estévez
authors.forename: Monica
authors.initials: M
authors.lastname: Borgatti
authors.forename: Roberto
authors.initials: R
authors.lastname: Gambari
mesh_terms: 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
chemical_list: D000178:Acrylamides; D000970:Antineoplastic Agents; D015107:4-Butyrolactone