title: Synthesis and biological evaluation of rebeccamycin analogues modified at the imide moiety.
abstract: Glycosylated indolocarbazoles related to the antibiotic rebeccamycin represent an important class of antitumour drugs. In the course of our structure-activity relationship studies, new rebeccamycin analogues modified at the imide moiety were synthesised. The antiproliferative activity of the compounds was evaluated on three human cancer cell lines, A2780 (ovarian cancer), H460 (lung cancer), and GLC4 (small-cell lung cancer). The in vitro cytotoxicity of compounds 2 and 4, characterised respectively by a 1,3-dioxolan and (1,3-dioxolan-4-yl)methylene groups linked to the imide moiety, was higher than the reference compound, edotecarin. The effect of compound 2 in inducing tumour regression in the A2780 xenograft model was also investigated.
authors: Menarini Ricerche Pomezia, via Tito Speri 10, 00040 Pomezia (Rome), Italy.
authors: Fabio
authors: F
authors: Animati
authors: Marco
authors: M
authors: Berettoni
authors: Mario
authors: M
authors: Bigioni
authors: Monica
authors: M
authors: Binaschi
authors: Amalia
authors: A
authors: Cipollone
authors: Clelia
authors: C
authors: Irrissuto
authors: Federica
authors: F
authors: Nardelli
authors: Lauso
authors: L
authors: Olivieri
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D002227:Carbazoles / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007094:Imides / Q000737:chemistry*; D051379:Mice; D010051:Ovarian Neoplasms / Q000188:drug therapy; D013329:Structure-Activity Relationship; D014183:Transplantation, Heterologous
chemical_list: D000970:Antineoplastic Agents; D002227:Carbazoles; D007094:Imides; C053339:rebeccamycin