Synthesis and anti-tumour activity of the spatially-separated mustard bis-N,N'-[3-(N-(2-chloroethyl)-N-ethyl)amino-5-[N,N-dimethylamino)methy l)-aminophenyl]-1,4-benzenedicarboxamide, which alkylates DNA exclusively at adenines in the minor groove

Anticancer Drug Des. 1991 Jul;6(3):195-206.

Abstract

The mustard derivative, bis-N,N'-[3-(N-(2-chloroethyl)-N-ethyl)amino-5- [N,N-dimethylamino)methyl)aminophenyl]-1,4-benzenedicarboxamide has been synthesized from 3-acetamido-5-nitrobenzoic acid in a 6-step procedure. This compound alkylates exclusively in the minor groove of DNA, at the N3 site of adenines occurring in sequences of runs of adenines and (to a small extent) at 5'-TA and 5'-AT sites. Gel electrophoresis studies and in vitro cytotoxicity assays against repair-deficient AA8 mutant cell lines show it has a high degree of DNA interstrand cross-linking ability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylating Agents / chemical synthesis*
  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Base Sequence
  • Cell Line
  • DNA Damage*
  • DNA, Bacterial / chemistry
  • Drug Design
  • In Vitro Techniques
  • Mice
  • Molecular Sequence Data
  • Nitrogen Mustard Compounds / chemical synthesis*
  • Nitrogen Mustard Compounds / pharmacology

Substances

  • Alkylating Agents
  • Antineoplastic Agents
  • DNA, Bacterial
  • Nitrogen Mustard Compounds