Fluorescent schweinfurthin B and F analogs with anti-proliferative activity.
Fluorescent schweinfurthin B and F analogs with anti-proliferative activity.
复制标题
具有抗增殖活性的荧光 schweinfurthin B 和 F 类似物。
DOI：
10.1016/j.bmc.2010.07.056
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发表时间：
2010
影响因子：
3.5
通讯作者：
Wiemer,DavidF
中科院分区：
文献类型：
--
作者：
Topczewski,JosephJ;Kuder,CraigH;Neighbors,JeffreyD;Hohl,RaymondJ;Wiemer,DavidF
在美国国家癌症研究所的 60 种细胞系筛选中，天然四环猪味素是细胞生长的有效且选择性抑制剂。目前，这种活性的机制或细胞靶标尚未确定，阐明猪蹄蛋白作用模式的努力将受益于开发可在细胞内轻松观察到的强效荧光类似物。该报告描述了猪肚菌 B 和 F 的荧光类似物的合成，并证明这些化合物保留了天然猪肚菌特有的针对特定人类癌细胞的有效且不同的毒性活性。此外，还描述了控制化合物的合成，这些化合物保持平行的荧光特性，但缺乏天然猪瘟的有效活性。荧光显微镜的使用显示了活性和相对无活性的猪威辛类似物的定位之间的差异。活性化合物定位于外周泪点，可识别活性位点。
The natural tetracyclic schweinfurthins are potent and selective inhibitors of cell growth in the National Cancer Institute’s 60 cell-line screen. At this time, the mechanism or cellular target that underlies this activity has not yet been identified, and efforts to illuminate the schweinfurthins’ mode of action would benefit from development of potent fluorescent analogs that could be readily visualized within cells. This report describes the synthesis of fluorescent analogs of schweinfurthins B and F, and demonstrates that these compounds retain the potent and differentially toxic activities against select human cancer cells that are characteristic of the natural schweinfurthins. In addition, the synthesis of control compounds that maintain parallel fluorescent properties, but lack the potent activity of the natural schweinfurthin is described. Use of fluorescence microscopy shows differences between the localization of the active and relatively inactive schweinfurthin analogs. The active compounds localize in peripheral puncta which may identify the site(s) of activity.