Cytotoxic activity of azulenes against human oral tumor cell lines

Anticancer Res. Nov-Dec 2003;23(6C):4747-55.


We investigated 27 azulene derivatives for their relative cytotoxicity against three human normal cells and three human oral tumor cell lines. 2-Acetylaminoazulene [4], diethyl 2-chlorozulene-1,3-dicarboxylate [9] and methyl 7-isopropyl-2-methoxyazulene-1-carboxylate [24] showed higher tumor-specific cytotoxicity than azulene [1] and guaiazulene [2]. Four 1- and 3-halogenated compounds showed lower tumor specificity. The tumor-specific cytotoxic activity seems not to be related to the position of functional groups. All compounds showed no anti-HIV activity. Methyl 7-isopropyl-2-methoxyazulene-1-carboxylate [24] induced apoptotic cell death (characterized by internucleosomal DNA fragmentation and caspase 3 activation) in HL-60 cells. ESR spectroscopy showed that methyl 7-isopropyl-2-methoxyazulene-1-carboxylate [24] did not produce radical and less efficiently scavenged O2- (generated by HX-XOD reaction) and NO (generated from NOC-7). These data suggest that a radical-mediated oxidation mechanism may not be involved in the apoptosis induction by methyl 7-isopropyl-2-methoxyazulene-1-carboxylate [24].

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / toxicity*
  • Apoptosis / drug effects*
  • Azulenes
  • Cell Line
  • Cell Survival / drug effects*
  • Cycloheptanes / chemistry*
  • Cycloheptanes / toxicity*
  • Electron Spin Resonance Spectroscopy
  • Humans
  • Molecular Structure
  • Mouth Neoplasms
  • Structure-Activity Relationship
  • Tumor Cells, Cultured


  • Anti-Inflammatory Agents, Non-Steroidal
  • Azulenes
  • Cycloheptanes
  • azulene