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: Y Li, J L Eiseman, D L Sentz, F A Rogers, S S Pan, L T Hu, M J Egorin, P S Callery
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 39 Issue 1 Pg. 339-41 (Jan 05 1996) ISSN: 0022-2623 [Print] United States
• PMID: 8568824 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• 1,12-diaziridinyl-4,9-diazadodecane
• Antineoplastic Agents
• Aziridines
• Cross-Linking Reagents
• Spermine
• Mechlorethamine
• aziridine
• DNA
• Thiotepa
• Melphalan

Topics

• Animals
• Antineoplastic Agents (administration & dosage, chemical synthesis, chemistry, pharmacology)
• Aziridines (administration & dosage, chemical synthesis, chemistry, pharmacology)
• Cross-Linking Reagents (chemical synthesis, pharmacology, toxicity)
• DNA (drug effects)
• Electrophoresis, Agar Gel
• Female
• Leukemia L1210 (drug therapy)
• Mechlorethamine (pharmacology)
• Melphalan (pharmacology)
• Mice
• Mice, Inbred Strains
• Spermine (administration & dosage, analogs & derivatives, chemical synthesis, chemistry, pharmacology)
• Thiotepa (pharmacology)