Potent antitumor mimetics of annonaceous acetogenins embedded with an aromatic moiety in the left hydrocarbon chain part.
Potent antitumor mimetics of annonaceous acetogenins embedded with an aromatic moiety in the left hydrocarbon chain part.
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DOI：
10.1021/jm101053k
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发表时间：
2011-01
影响因子：
7.3
通讯作者：
Qicai Xiao;Yongqiang Liu;Yatao Qiu;Guangbiao Zhou;Chan Mao;Zheng Li;Z. Yao;Sheng Jiang
中科院分区：
文献类型：
--
作者：
Qicai Xiao;Yongqiang Liu;Yatao Qiu;Guangbiao Zhou;Chan Mao;Zheng Li;Z. Yao;Sheng Jiang
番荔枝内酯是一类天然存在的具有显著抗癌活性的聚酮化合物。第一代番荔枝内酯模拟物（1，AA 005）显示出与天然产物相当的活性，并在癌细胞和正常细胞之间表现出更高的选择性。在这项工作中，我们报告了一系列新的化合物1类似物的设计，合成和评价，其中各种构象受限的片段嵌入在左烃链部分。带有联苯部分的化合物7被鉴定为表现出更有效的抗增殖活性，并且相对于正常细胞优先靶向癌细胞，因此代表了进一步优化的新先导。
Annonaceous acetogenins are a large family of naturally occurring polyketides exhibiting remarkable anticancer activities. The first generation of annonaceous acetogenin mimetic (1, AA005) exhibits comparable activity as that of natural products and presents much higher selectivity between cancer and normal cells. In this work, we report the design, synthesis, and evaluation of a new series of compound 1 analogues in which a variety of conformation-constrained fragments were embedded in the left hydrocarbon chain part. Compound 7 bearing a biphenyl moiety was identified to exhibit more potent antiproliferative activity and preferentially target cancer cells over normal cells and thus represents a new lead for further optimization.