title: Synthesis and antitumor evaluation of a highly potent cytotoxic DNA cross-linking polyamine analogue, 1,12-diaziridinyl-4,9-diazadodecane.
abstract: A diaziridinylspermine analogue, 1,12-diaziridinyl-4,9-diazadodecane (NSC-667005), was synthesized as a bisalkylating agent with a polyamine backbone. DNA cross-linking was detected in the reaction of linearized pBR322 DNA with 1,12-diaziridinyl-4,9-diazadodecane at concentrations comparable with that required for cross-linking by two nitrogen mustard drugs, mechlorethamine and melphalan. A significant increase in life span of female CD2F1 mice bearing L1210 murine leukemia was observed after intravenous administration of 1,12-diaziridinyl-4,9-diazadodecane in doses of less than 2.7 mg/kg, given on days 1, 5, and 9 of treatment.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland Cancer Center, Baltimore, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: J L
authors.initials: JL
authors.lastname: Eiseman
authors.forename: D L
authors.initials: DL
authors.lastname: Sentz
authors.forename: F A
authors.initials: FA
authors.lastname: Rogers
authors.forename: S S
authors.initials: SS
authors.lastname: Pan
authors.forename: L T
authors.initials: LT
authors.lastname: Hu
authors.forename: M J
authors.initials: MJ
authors.lastname: Egorin
authors.forename: P S
authors.initials: PS
authors.lastname: Callery
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001388:Aziridines / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D003432:Cross-Linking Reagents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D004247:DNA / Q000187:drug effects*; D004587:Electrophoresis, Agar Gel; D005260:Female; D007939:Leukemia L1210 / Q000188:drug therapy; D008466:Mechlorethamine / Q000494:pharmacology; D008558:Melphalan / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D013096:Spermine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013852:Thiotepa / Q000494:pharmacology
chemical_list: C097784:1,12-diaziridinyl-4,9-diazadodecane; D000970:Antineoplastic Agents; D001388:Aziridines; D003432:Cross-Linking Reagents; D013096:Spermine; D008466:Mechlorethamine; C033132:aziridine; D004247:DNA; D013852:Thiotepa; D008558:Melphalan