title: Synthesis and antitumor evaluation of bis aza-anthracene-9,10-diones and bis aza-anthrapyrazole-6-ones.
abstract: The good results obtained as potential antitumor drugs with aza-anthracenediones and aza-anthrapyrazoles, e.g. pixantrone, 1a, and 1b (Chart 1), prompted us to design and synthesize a series of symmetrical bis derivatives, compounds 7-10 (Chart 1). These compounds are dimers of different aza-anthracenedione and aza-anthrapyrazolone monomers connected by the linker found to be the most appropriate among potential bis intercalators synthesized by us. The DNA-binding properties of bis derivatives 7 and 8 have been examined using fluorometric techniques: these target compounds are excellent DNA ligands, with a clear binding site preference for AT-rich duplexes. In vitro cytotoxic activity of all target compounds 7-10 and of reference compound pixantrone toward human cancer adenocarcinoma cell line HT29 is also described. Two selected compounds have been investigated for their capacity of inducing early apoptosis.
authors.affiliation: Department of Chemical Sciences, University of Camerino, Via S. Agostino 1, 62032 Camerino, Italy. ippolito.antonini@unicam.it
authors.forename: Ippolito
authors.initials: I
authors.lastname: Antonini
authors.forename: Giorgio
authors.initials: G
authors.lastname: Santoni
authors.forename: Roberta
authors.initials: R
authors.lastname: Lucciarini
authors.forename: Consuelo
authors.initials: C
authors.lastname: Amantini
authors.forename: Diego
authors.initials: D
authors.lastname: Dal Ben
authors.forename: Rosaria
authors.initials: R
authors.lastname: Volpini
authors.forename: Gloria
authors.initials: G
authors.lastname: Cristalli
mesh_terms: D000873:Anthracenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004247:DNA / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D020869:Gene Expression Profiling; D019073:HT29 Cells; D006801:Humans; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis
chemical_list: D000873:Anthracenes; D000970:Antineoplastic Agents; D001372:Aza Compounds; D011720:Pyrazoles; D012333:RNA, Messenger; D004247:DNA