5-炔基-2'-脱氧尿苷：无色谱法合成及对人乳腺癌细胞的细胞毒性评估
5-Alkynyl-2'-deoxyuridines: chromatography-free synthesis and cytotoxicity evaluation against human breast cancer cells.
作者信息
Meneni Srinivasarao, Ott Ingo, Sergeant Craig D, Sniady Adam, Gust Ronald, Dembinski Roman
机构信息
Department of Chemistry and Center for Biomedical Research, Oakland University, 2200 N. Squirrel Rd., Rochester, MI 48309-4477, USA.
出版信息
Bioorg Med Chem. 2007 Apr 15;15(8):3082-8. doi: 10.1016/j.bmc.2007.01.048. Epub 2007 Feb 1.
Abstract
Starting with 5-iodo-2'-deoxyuridine, a series of 5-alkynyl-2'-deoxyuridines (with n-propyl, cyclopropyl, 1-hydroxycyclohexyl, p-tolyl, p-tert-butylphenyl, p-pentylphenyl, and trimethylsilyl alkyne substituents) have been synthesized via the palladium-catalyzed (Sonogashira) coupling reaction followed by a simplified isolation protocol (76-94% yield). The cytotoxic activity of modified nucleosides against MCF-7 and MDA-MB-231 human breast cancer cells has been determined in vitro. 5-Ethynyl-2'-deoxyuridine, the only nucleoside in the series containing a terminal acetylene, is the most potent inhibitor with IC(50) (microM) 0.4+/-0.3 for MCF-7 and 4.4+/-0.4 for MDA-MB-231.
摘要
从5-碘-2'-脱氧尿苷开始，通过钯催化（Sonogashira）偶联反应，随后采用简化的分离方案（产率76 - 94%），合成了一系列5-炔基-2'-脱氧尿苷（具有正丙基、环丙基、1-羟基环己基、对甲苯基、对叔丁基苯基、对戊基苯基和三甲基硅烷基炔取代基）。已在体外测定了修饰核苷对MCF-7和MDA-MB-231人乳腺癌细胞的细胞毒性活性。5-乙炔基-2'-脱氧尿苷是该系列中唯一含有末端乙炔的核苷，是最有效的抑制剂，对MCF-7的IC(50)（微摩尔）为0.4±0.3，对MDA-MB-231为4.4±0.4。
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