Structure and activity of largazole, a potent antiproliferative agent from the Floridian marine cyanobacterium Symploca sp.
Structure and activity of largazole, a potent antiproliferative agent from the Floridian marine cyanobacterium Symploca sp.
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DOI：
10.1021/ja7110064
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发表时间：
2008-02-13
影响因子：
15
通讯作者：
Luesch, Hendrik
中科院分区：
文献类型：
--
作者：
Taori, Kanchan;Paul, Valerie J.;Luesch, Hendrik
从采集于佛罗里达群岛的海洋蓝细菌Symploca sp.中分离出一种新的细胞毒性环缩酚酸肽，称为largazole（1）。其平面结构通过一维和二维NMR光谱结合质谱进行了阐明。通过化学降解，然后通过手性HPLC分析确定I的绝对构型。Largazole（1）具有密集组装的不寻常的结构特征，包括罕见的4-甲基噻唑啉线性稠合到噻唑的环状核心和迄今未描述的3-羟基-7-巯基庚-4-烯酸单元纳入酯，硫酯和酰胺框架。Largazole（1）具有强效抗增殖活性，优先靶向癌细胞而非非转化细胞。
A novel cytotoxic cyclodepsipeptide, termed largazole (1), has been isolated from the marine cyanobacterium Symploca sp. collected in the Florida Keys. Its planar structure was elucidated by 1 D and 2D NMR spectroscopy in conjunction with mass spectrometry. The absolute configuration of I was determined by chemical degradation followed by chiral HPLC analysis. Largazole (1) possesses densely assembled unusual structural features, including a rare 4-methylthiazoline linearly fused to a thiazole in its cyclic core and a hitherto undescribed 3-hydroxy-7-mercaptohept-4-enoic acid unit incorporated in an ester, thioester, and amide framework. Largazole (1) exhibits potent antiproliferative activity and preferentially targets cancer cells over nontransformed cells.