Synthesis, physicochemical characterization and preliminary pharmacological in vitro evaluation of two novel cytotoxic benzophenone-linked 3,3-dimethyltriazenes

Pharmazie. 2006 Jun;61(6):511-6. doi: 10.1002/chin.200639088.

Abstract

The synthesis, physicochemical characterization and preliminary pharmacological evaluation of the cytotoxic effects of two novel substances, 1-(4-benzoylphenyl)-3,3-dimethyltriazene and 1-(2-benzoylphenyl)-3,3-dimethyltriazene is presented. The cytotoxicity of the novel benzophenone-linked triazenes and of ten other 1-phenyl-3,3-dimethyl triazene derivatives as well as of the referent alkylating drug melphalan was assessed using the MTT-dye reduction assay. A panel of human tumor cell lines was used: the chronic lymphoid leukemia SKW-3, the acute promyelocyte leukemia HL-60 and its multi-drug-resistant subline HL-60/Dox. Both novel compounds showed strong cytotoxic activity, comparable to that of the referent alkylating agent melphalan, whereas the ten ring-substituted 1-phenyl-3,3-dimethyl triazenes proved to be far less active in vitro. DNA-fragmentation analysis indicated that after 24 h treatment the novel benzophenone-linked triazenes induced programmed cell death in HL-60 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Benzophenones / chemical synthesis*
  • Benzophenones / pharmacology*
  • Cell Line
  • Chemical Phenomena
  • Chemistry, Physical
  • DNA Fragmentation / drug effects
  • DNA, Neoplasm / biosynthesis
  • HL-60 Cells
  • Humans
  • Models, Molecular
  • Structure-Activity Relationship
  • Tetrazolium Salts
  • Thiazoles
  • Triazenes / chemical synthesis*
  • Triazenes / pharmacology*

Substances

  • Antineoplastic Agents
  • Benzophenones
  • DNA, Neoplasm
  • Tetrazolium Salts
  • Thiazoles
  • Triazenes
  • thiazolyl blue