5-alkynyl-2′-deoxyuridines:: Chromatography-free synthesis and cytotoxicity evaluation against human breast cancer cells
5-alkynyl-2′-deoxyuridines:: Chromatography-free synthesis and cytotoxicity evaluation against human breast cancer cells
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DOI：
10.1016/j.bmc.2007.01.048
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发表时间：
2007-04-15
影响因子：
3.5
通讯作者：
Dembinski, Roman
中科院分区：
文献类型：
--
作者：
Meneni, Srinivasarao;Ott, Ingo;Dembinski, Roman
以5-碘-2′-脱氧尿嘧啶为起始原料，通过钯催化（Sonogashira）偶联反应和简化的分离程序合成了一系列5-炔基-2′-脱氧尿嘧啶（含正丙基、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基炔取代基）。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活性。5-乙基-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，其IC50 （μ M）对MCF-7为0.4 +/- 0.3，对MDA-MB-231为4.4 +/- 0.4。(c) 2007 Elsevier Ltd.版权所有。
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 IC50 (mu M) 0.4 +/- 0.3 for MCF-7 and 4.4 +/- 0.4 for MDA-MB-231. (c) 2007 Elsevier Ltd. All rights reserved.