Halenaquinone and xestoquinone derivatives, inhibitors of Cdc25B phosphatase from a Xestospongia sp.

被引:72
作者
Cao, SG
Foster, C
Brisson, M
Lazo, JS
Kingston, DGI
机构
[1] Virginia Polytech Inst & State Univ, Dept Chem, Blacksburg, VA 24061 USA
[2] Univ Pittsburgh, Dept Pharmacol, Pittsburgh, PA 15260 USA
关键词
Cdc25; natural products; quinones;
D O I
10.1016/j.bmc.2004.11.039
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Separation of an extract of a Xestospongia sp., guided by bioassay against Cdc25B, led to the isolation of nine compounds, halenaquinone (1), xestoquinone (2), adociaquinones A (3) and B (4), 3-ketoadociaquinones A (5) and B (6), tetrahydrohalenaquinones A (7) and B (8), and 13-O-methyl xestoquinol sulfate (9). The structures of the new natural products 6 and 9 were established on the basis of extensive one- and two-dimensional NMR studies. Compounds 1, 4, and 6 inhibited recombinant human Cdc25B in vitro with IC50 values of 0.7, 0.07, and 0.2 muM, respectively, and were 19- to 150-fold less active against two related protein phosphatases. Compound 4 blocked cell cycle progression through mitosis. (C) 2004 Elsevier Ltd. All rights reserved.
引用
收藏
页码:999 / 1003
页数:5
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