Phenylbenzopyrones structure-activity studies identify betuletol derivatives as potential antitumoral agents

Eur J Pharmacol. 2006 Oct 24;548(1-3):9-20. doi: 10.1016/j.ejphar.2006.07.020. Epub 2006 Jul 22.


We have analyzed the cytotoxicity of 22 compounds with a phenylbenzo-gamma-pirone core structure, most of them obtained from natural sources, in five human tumor cell lines (HL-60, A431, SK-OV-3, HeLa and HOS). Betuletol 3-methyl ether and its diacetate were the most cytotoxic compounds. The HL-60 cell line was especially sensitive to these compounds, with IC50 values of approximately 1 microM. Treatment of HL-60 cells with betuletol 3-methyl ether was associated with apoptosis induction which was prevented by a non-specific caspase inhibitor (z-VAD-fmk) and also by a specific inhibitor of caspase-8 (z-IETD-fmk) indicating activation of the extrinsic apoptotic pathway. The results suggest that betuletol 3-methyl ether has potential as new anticancer agent.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Caspases / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cytochromes c / metabolism
  • DNA Fragmentation
  • Ethers / pharmacology*
  • Flavonoids / pharmacology*
  • Humans
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Poly(ADP-ribose) Polymerases / metabolism
  • Structure-Activity Relationship


  • Antineoplastic Agents
  • Ethers
  • Flavonoids
  • betuletol 3-methyl ether
  • Cytochromes c
  • Poly(ADP-ribose) Polymerases
  • Caspases