title: Synthesis and DNA-cleaving activity of lactenediynes conjugated with DNA-complexing moieties.
abstract: Lactenediynes are compounds characterized by the fusion of a beta-lactam with a cyclodeca-3-ene-1,5-diyne. In this work the most promising members of this family have been activated by attaching a carbalkoxy or a carbamoyl group to the azetidinone nitrogen, and conjugated to various DNA-complexing moieties, either acting by intercalation or through groove binding. These conjugated artificial enediynes have been demonstrated to possess in vitro ability to produce single and double strand cleavage of plasmid DNA. As potency and capacity to induce double cut, they rank among the best simple enediyne analogues ever prepared. A thorough investigation was carried out in order to develop the best suited linkers for assembling these conjugates.
authors.affiliation: Dipartimento di Chimica e Chimica Industriale, via Dodecaneso 31, I-16146 Genova, Italy. banfi@chimica.unige.it
authors.forename: Luca
authors.initials: L
authors.lastname: Banfi
authors.forename: Andrea
authors.initials: A
authors.lastname: Basso
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bevilacqua
authors.forename: Valentina
authors.initials: V
authors.lastname: Gandolfo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Giannini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Guanti
authors.forename: Loana
authors.initials: L
authors.lastname: Musso
authors.forename: Monica
authors.initials: M
authors.lastname: Paravidino
authors.forename: Renata
authors.initials: R
authors.lastname: Riva
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000737:chemistry* / Q000235:genetics*; D053281:Enediynes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007783:Lactones / Q000737:chemistry*; D015394:Molecular Structure; D010957:Plasmids / Q000737:chemistry / Q000235:genetics; D013329:Structure-Activity Relationship
chemical_list: D053281:Enediynes; D007783:Lactones; D004247:DNA