Cancer preventive agents 9. Betulinic acid derivatives as potent cancer chemopreventive agents.
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 10mol ratio/TPA, respectively, with IC(50) value of 285mol ratio/32pmol TPA). Compound 6 merits further development as a cancer preventive agent.
Nakagawa-Goto
Kyoko
K
Natural Products Research Laboratories, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA.
Yamada
Koji
K
Taniguchi
Masahiko
M
Tokuda
Harukuni
H
Lee
Kuo-Hsiung
KH
D016588:Anticarcinogenic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000956:Antigens, Viral / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D004951:Esterification; D006801:Humans; D053978:Pentacyclic Triterpenes; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014315:Triterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000094062:Betulinic Acid
D016588:Anticarcinogenic Agents; D000956:Antigens, Viral; C033305:Epstein-Barr virus early antigen; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D013755:Tetradecanoylphorbol Acetate; D000094062:Betulinic Acid