Cytotoxic activity of azulenequinones against human oral tumor cell lines

Anticancer Res. 2005 Jan-Feb;25(1A):305-12.


We investigated twenty-seven azulenequinone derivatives for their relative cytotoxicity against three human normal cell lines (HGF, HPC, HPLF) and four human tumor cell lines (HSG, HSC-2, HSC-3, HL-60). Parent 1,5-azulenequinone showed potent and some tumor-specific cytotoxicity. Halogenated derivatives of 1,5- and 1,7-azulenequinone showed potent cytotoxicity, but lower tumor-specific cytotoxicity. In contrast to other azulenequinones, amino derivatives such as 3-amino-1,5- and 1, 7-azulenequinones showed relatively lower cytotoxic activity. The 3-Phenoxy-1,5-azuleneqinone derivative showed higher cytotoxicity than the 3-phenoxy-1, 7-azulenequinone derivative. 1,5- and 1,7-Azulenequinones generally showed higher cytotoxicity, as compared with tropolones and azulene derivatives. 3- (3-Guaiazulenyl)-1, 5-azulenequinone [12] and 7-isopropyl-3- (4-methylanilino)-2-methyl- 1, 5-azulenequinone [24] showed a relatively higher TS value and induced apoptosis (internucleosomal DNA fragmentation, activation of caspases 3, 8 and 9) in HL-60 and HSC-2 cells, possibly via the activation of both mitochondria-independent (extrinsic) and -dependent (intrinsic) pathways. Western blot analysis showed that [24] slightly increased the intracellular concentration of pro-apoptotic proteins (Bad, Bax) in HSC-2 cells, whereas [12] was much less active. None of the twenty-seven azulenequinones showed anti-HIV activity. These results suggest [12] and [24] as possible candidates for future cancer chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / pharmacology
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Azulenes
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cycloheptanes / pharmacology*
  • Drug Screening Assays, Antitumor
  • HIV Infections / drug therapy
  • HIV-1
  • HL-60 Cells
  • Humans
  • Mouth Neoplasms / drug therapy*
  • Mouth Neoplasms / pathology
  • Quinones / pharmacology*
  • Structure-Activity Relationship


  • Anti-HIV Agents
  • Antineoplastic Agents
  • Azulenes
  • Cycloheptanes
  • Quinones
  • azulene