New cytotoxic annonaceous acetogenin mimetics having a nitrogen-heterocyclic terminal and their application to cell imaging
New cytotoxic annonaceous acetogenin mimetics having a nitrogen-heterocyclic terminal and their application to cell imaging
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具有氮杂环末端的新型细胞毒性番石榴苷模拟物及其在细胞成像中的应用
DOI：
10.1016/j.tet.2014.05.047
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发表时间：
2014-08-19
期刊：
影响因子：
2.1
通讯作者：
Yao, Zhu-Jun
中科院分区：
文献类型：
--
作者：
Chen, Yi-Jie;Jin, Sheng;Yao, Zhu-Jun
通常认为末端不饱和内酯或其等效物对于天然番荔枝内酯及其人工模拟物的细胞毒性至关重要。本研究首次发现了一系列具有细胞毒性的含乙二醇醚的模拟物，其中引入了多种简单的脂肪族氮杂环取代了我们先前研究中鉴定的具有代表性的生物活性聚醚模拟物AA 005（1）的内酯末端。其中，发现带有末端哌嗪的模拟物4是对抗三种癌细胞增殖的最有效的化合物。基于我们的新发现，还开发了荧光探针7，并成功应用于癌细胞的成像。这项工作为开发天然番荔枝内酯类化合物的简单细胞毒性模拟物和生物成像的分子工具提供了新的策略。(C)2014爱思唯尔有限公司版权所有。
A terminal unsaturated lactone or its equivalent is commonly believed to be essential for the cytotoxicity of natural annonaceous acetogenins and their artificial mimetics. In this work, we discovered a series of new cytotoxic ethylene glycol ether-containing mimetics, in which a variety of simple aliphatic nitrogen-heterocycles were introduced to replace the lactone terminal of AA005 (1), a representative bioactive polyether mimic identified from our previous research, for the first time. Among these, mimic 4 bearing a terminal piperazine was found to be the most potent compound against the proliferation of three cancer cells. Based on our new findings, a fluorescent probe 7 was also developed and successfully applied to the imaging of cancer cells. This work provides a new strategy for developing simpler cytotoxic mimetics of natural annonaceous acetogenins and molecular tools for biological imaging. (C) 2014 Elsevier Ltd. All rights reserved.