Synthesis and properties of bifunctional chloroalkyl nitrosamines with an intercalating moiety

Satoko Ishikawa, Megumi Tajima, Masataka Mochizuki

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Three N-nitroso-N-(arylcarbonyloxymethyl)-3-chloropropylamines were synthesized, and their chemical and biological properties were studied. All arylcarboxylates intercalated with double-stranded DNA, and their mutagenicity and DNA cross-linking activity were affected by their ring structure. The DNA interstrand cross-link formation increased dose dependently after treatment with the acridine analog. The anthraquinone analog showed the highest bacterial mutagenicity among the three nitrosamines in Salmonella typhimurium TA100, while in Salmonella typhimurium TA92, which can detect cross-linking agents, the acridine analog showed the highest mutagenicity. This agreed with the result of a cross-linking assay. These results suggest that the three-ring aromatic moiety gives DNA-intercalating ability to cross-linkable chloropropyl nitrosamine, and the acridine analog is considered as a possible new antitumor lead compound.

Original languageEnglish
Pages (from-to)3791-3796
Number of pages6
JournalBioorganic and Medicinal Chemistry
Volume12
Issue number14
DOIs
Publication statusPublished - 2004 Jul 15

Keywords

  • Antitumor agent
  • DNA cross-link
  • Nitrosamine

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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