SYNTHESIS AND ANTITUMOR EVALUATION OF A HIGHLY POTENT CYTOTOXIC DNA CROSS-LINKING POLYAMINE ANALOG, 1,12-DIAZIRIDINYL-4,9-DIAZADODECANE

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 linearize d pBR322 DNA with 1,12-diaziridinyl-4,9-diazadodecane at concentration s comparable with that required for cross-linking by two nitrogen must ard drugs, mechlorethamine and melphalan. A significant increase in li fe span of female CD2F1 mice bearing L1210 murine leukemia was observe d after intravenous administration of 1,12-diaziridinyl-4,9-diazadodec ane in doses of less than 2.7 mg/kg, given on days 1, 5, and 9 of trea tment.