Cancer Preventive Agents 9. Betulinic Acid Derivatives as Potent Cancer Chemopreventive Agents †

摘要

C-3 Esterifications of betulinic acid (BA, >1) and its A-ring homolog, ceanothic acid (CA, >2), were carried out to provide sixteen terpenoids, >4-19, including nine new compounds (>4-12). All synthesized compounds were evaluated in an in vitro antitumor-promoting assay using the Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. Among them, compounds >4-6, 11-14, 16, and >17 displayed remarkable inhibitory effects of EBV-EA activation. BA analog >6, which contains a prenyl-like group, showed the most potent inhibitory effect (100, 76, 37, and 11% inhibition of EBA activation at 1000, 500, 100 and 10 mol ratio/TPA, respectively, with IC50 value of 285 mol ratio/32pmol TPA). Compound >6 merits further development as a cancer preventive agent.