Planta Med 2008; 74 - PG78
DOI: 10.1055/s-0028-1084830

Structure-Activity relationship of sesquiterpenes dihydro-β-agarofuran as chemopreventive agents

NR Perestelo 1, IA Jiménez 1, H Tokuda 2, IL Bazzocchi 1
  • 1Instituto Universitario de Bio-Orgánica „Antonio González“, Universidad de La Laguna, Avda. Astrofísico Fco. Sánchez 2, La Laguna, 38206 Tenerife, Spain
  • 2Kyoto Prefectural University of Medicine, Kamigyo-Ku, Kyoto 602–0841, Japan

Species of the Celastraceae family have a long history of use in traditional medicine, especially in Asia and Latin America. Sesquiterpene esters, based on the dihydro-β-agarofuran skeleton, are considered to be chemotaxonomic indicators of this family and they have attracted considerable interest on account of their wide range of biological activities. These data along with their structural characteristics have led them to be considered as „privileged structures“[1].

Inhibition of the tumor promotion stage in the multistage of chemical carcinogenesis has been regarded as a promising strategy for cancer chemoprevention. In the search for cancer chemopreventive agents, the inhibition of Epstein-Barr virus early antigen (EBV-EA) induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) has been developed as a primary screening test [2].

As part of an intensive study of the bioactive metabolites from species of Celastraceae, we report herein the antitumor-promoting effects on EBV-EA in Raji cells of twenty sesquiterpenes, with a 1,2,3,6,8,15-hexasubstituted 4β-hydroxydihydro-β-agarofuran skeleton, isolated from Crossopetalum tonduzii. Five of the compounds showed strong inhibitory activity (90–96% inhibition at 10 mol ratio/TPA), higher than that of β-carotene, which is known as a typical antitumor promoter.

The structure-activity relationship (SAR) study suggests than the presence of an acetate group at C-1 plays an important role in the inhibitory activity, whereas the nicotinate moieties decrease the activity.

Acknowledgements: We are indebted to the DGES (CTQ2006–13376/BQU) and FICIC (01/2007) projects for financial support. N.R.P. thanks to the Gobierno Autónomo de Canarias for a fellowship.

References: 1. Gao, J-M., Wu, W-J. (2007) Nat. Prod. Rep. 24: 1153.

2. Akihisa T., K Yasukawa. (2003) Studies in Natural Products Chemistry: Bioactive Natural Products, Ed. Atta-ur Rahman, Elsevier Science Publisher, Amsterdam.