Structure-activity relationships of quassinoids for eukaryotic protein synthesis

被引：50

作者：

Fukamiya, N

Lee, KH

Muhammad, I

Murakami, C

Okano, M

Harvey, I

Pelletier, J

机构：

[1] McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada

[2] McGill Univ, McGill Canc Ctr, Montreal, PQ H3G 1Y6, Canada

[3] Hiroshima Univ, Fac Integrated Arts & Sci, Hiroshima 7398521, Japan

[4] Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, Chapel Hill, NC 27599 USA

[5] Univ Mississippi, Sch Pharm, Pharmaceut Sci Res Inst, Natl Ctr Nat Prod Res, University, MS 38677 USA

来源：

CANCER LETTERS | 2005年 / 220卷 / 01期

关键词：

protein synthesis inhibitor; translation; quassinoid; structure-activity relationships;

D O I：

10.1016/j.canlet.2004.04.023

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

The effect of 63 quassinoids on eukaryotic protein synthesis has been investigated. Seventeen of the tested compounds showed potent in vitro activity, with IC(50)s below 2 mu M for inhibition in Krebs ascites translation extracts. Sixteen of these quassinoids were also potent inhibitors of in vivo protein synthesis when exposed to Hela cells for 1 h. Our results led to the following structure-activity relationships for quassinoids regarding translation inhibition. Activity is influenced by (i) the nature of the C-15 side chain, (ii) the nature of A ring modifications, (iii) the presence or absence of a sugar moiety, and (iv) the presence of an epoxymethano bridge. (c) 2004 Elsevier Ireland Ltd. All rights reserved.

引用

页码：37 / 48

页数：12

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