Cancer preventive agents 9. Betulinic acid derivatives as potent cancer chemopreventive agents

被引：42

作者：

Nakagawa-Goto, Kyoko ^{[1
]}

Yamada, Koji ^{[1
]}

Taniguchi, Masahiko ^{[1
]}

Tokuda, Harukuni ^{[2
]}

Lee, Kuo-Hsiung ^{[1
]}

机构：

[1] Univ N Carolina, Nat Prod Res Labs, Eshelman Sch Pharm, Chapel Hill, NC 27599 USA

[2] Kyoto Prefectural Univ Med, Dept Biochem, Kyoto 6020841, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 13期

关键词：

Betulinic acid; Ceanothic acid; Antitumor-promoter; Cancer preventive agents; Epstein-Barr virus; ANTI-AIDS AGENTS; TRITERPENE ACIDS; IN-VITRO; ACTIVATION; APOPTOSIS;

D O I：

10.1016/j.bmcl.2009.05.050

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

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 (EBVEA) 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/32 pmol TPA). Compound 6 merits further development as a cancer preventive agent. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：3378 / 3381

页数：4

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