title: Cytotoxic and DNA binding properties of aminoalkyl derivatives of di- and triazaphenanthrenes.
abstract: A series of mono- and dicationic derivatives of various di- and triazaphenanthrenes were synthesized and evaluated against both wild-type and amsacrine-resistant P388 leukemia in vitro. Monocationic derivatives of the fully-aromatic benzo[c][1,8]naphthyridine chromophore showed moderate and equal cytotoxicity in both cell lines, suggestive of efficacy against both the alpha and beta isozymes of mammalian DNA topoisomerase II. Derivatives of both the benzo[c][1,8]naphthyridine and benzo[c][1,8]naphthyridine-3(4H)-one chromophores also showed significant in vivo activity against wild-type P388 leukemia.
authors.affiliation: Chemistry Department, La Trobe University, Bundoora, Victoria, Australia.
authors.forename: G
authors.initials: G
authors.lastname: Argiropoulos
authors.forename: M R
authors.initials: MR
authors.lastname: Bates
authors.forename: P
authors.initials: P
authors.lastname: Cherubim
authors.forename: L W
authors.initials: LW
authors.lastname: Deady
authors.forename: A M
authors.initials: AM
authors.lastname: Ganakas
authors.forename: B C
authors.initials: BC
authors.lastname: Baguley
authors.forename: W A
authors.initials: WA
authors.lastname: Denny
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D001372:Aza Compounds / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D004249:DNA Damage; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D007546:Isoquinolines / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D007941:Leukemia P388 / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D009287:Naphthyridines / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D009368:Neoplasm Transplantation; D010616:Phenanthrenes / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D001372:Aza Compounds; D007364:Intercalating Agents; D007546:Isoquinolines; D009287:Naphthyridines; D010616:Phenanthrenes; D004247:DNA