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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antineoplastic Agents / administration & dosage
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Aziridines / administration & dosage
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Aziridines / chemical synthesis*
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Aziridines / chemistry
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Aziridines / pharmacology*
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Cross-Linking Reagents / chemical synthesis*
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Cross-Linking Reagents / pharmacology
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Cross-Linking Reagents / toxicity
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DNA / drug effects*
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Electrophoresis, Agar Gel
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Female
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Leukemia L1210 / drug therapy
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Mechlorethamine / pharmacology
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Melphalan / pharmacology
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Mice
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Mice, Inbred Strains
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Spermine / administration & dosage
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Spermine / analogs & derivatives*
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Spermine / chemical synthesis
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Spermine / chemistry
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Spermine / pharmacology
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Thiotepa / pharmacology
Substances
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1,12-diaziridinyl-4,9-diazadodecane
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Antineoplastic Agents
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Aziridines
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Cross-Linking Reagents
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Spermine
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Mechlorethamine
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aziridine
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DNA
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Thiotepa
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Melphalan