Synthesis and Biological Evaluations of Click-Generated Nitrogen Mustards

Nucleosides Nucleotides Nucleic Acids. 2015;34(7):500-14. doi: 10.1080/15257770.2015.1017580.

Abstract

This paper describes the synthesis of new click-generated nitrogen mustards and their biological evaluation. By using the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction, we managed to synthesize eight new nitrogen mustards. This strategy paves the way for the synthesis of a new family of nitrogen mustard, with an important structural variability. Furthermore, we studied the biological activity of synthesized compounds by testing their cytotoxicity on four representative cancer cell lines A431, JURKAT, K562, and U266. One structure, 1-benzyl-4-(N,N-di-2-chloroethylaminomethyl)-1H-[1,2,3]triazole, showed an interesting cytotoxic effect.

Keywords: CuAAC reaction; MTT assays; Nitrogen mustards; click chemistry.

MeSH terms

  • Alkynes / chemistry
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology*
  • Azides / chemistry
  • Catalysis
  • Click Chemistry*
  • Copper / chemistry
  • Cycloaddition Reaction
  • Cytotoxins / chemical synthesis*
  • Cytotoxins / pharmacology*
  • Humans
  • Mechlorethamine / analogs & derivatives*
  • Mechlorethamine / chemical synthesis*
  • Mechlorethamine / pharmacology
  • Neoplasms / drug therapy*
  • Tumor Cells, Cultured

Substances

  • Alkynes
  • Antineoplastic Agents
  • Azides
  • Cytotoxins
  • Mechlorethamine
  • Copper