Antitumor-promoting effects and cytotoxic activities of dammar resin triterpenoids and their derivatives.

Nineteen known triterpenoids, 1–19, and one known sesquiterpenoid, 20, were isolated from dammar resin obtained from Shorea javanica K. & V. (Dipterocarpaceae). One of the acidic triterpenoids, dammarenolic acid (1), was converted to fourteen derivatives, namely, an alcohol, 21, an aldehyde, 22, and twelve L-amino acid conjugates, 23–34. Compounds 1–34 were examined for their inhibitory effects on the induction of Epstein–Barr virus early antigen (EBV-EA) by 12-O-tetradecanoylphorbol 13-acetate (TPA) in Raji cells, a known primary screening test for antitumor promoters. All of the compounds tested, except for compounds 4, 5, 12–14, 16, and 17, showed inhibitory effects against EBV-EA activation with potencies either comparable with or stronger than that of β-carotene, a known natural antitumor promoter. In addition, (20S)-20-hydroxy-3,4-secodammara-4(28),24-dien-3-al (22) exhibited inhibitory effects on skin tumor promotion in an in vivo two-stage mouse skin carcinogenesis test based on 7,12-dimethylbenz[a]anthracene (DMBA) as initiator, and with TPA as promoter. Furthermore, evaluation of the cytotoxic activities of compounds 1–34 against human cancer cell lines showed that reduction (i.e., 21 and 22) or conjugation with L-amino acids (i.e., 23–34) of compound 1 enhanced the cytotoxicity against human melanoma cell line CRL1579.