Synthesis and structure-activity relationships studies of brartemicin analogs as anti-invasive agents
Synthesis and structure-activity relationships studies of brartemicin analogs as anti-invasive agents
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DOI：
10.1038/ja.2013.37
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发表时间：
2013-09-01
影响因子：
3.3
通讯作者：
Liu, Zhao-Peng
中科院分区：
文献类型：
--
作者：
Jiang, Yong-Li;Miyanaga, Satoshi;Liu, Zhao-Peng
Brartemicin是一种以海藻糖为基础的肿瘤细胞侵袭抑制剂，由Nonomuraea属放线菌产生。为了寻找更有效的抗侵袭剂并研究其构效关系，以α，α-D-海藻糖为原料，通过两条合成路线合成了19个青蒿素类似物，并对其抗侵袭活性进行了评价。化合物4f，6，6‘-双(2，3-二甲氧基苯甲酰基)-α，α-D-海藻糖比天然青蒿素更有效。对小鼠结肠26-L5、结肠癌SW620、黑色素瘤B16-BL6和乳腺MDA-MB-231细胞的IC50值分别为0.15、2.35、4.12和2.61mU。类似物4P，6，6‘-双(3，4-二甲氧基肉桂酰基)-α，α-D-海藻糖在体外对小鼠结肠26-L5癌细胞的侵袭作用与青蒿素相当。总结了这些基于海藻糖的新型化合物的构效关系。
Brartemicin is a trehalose-based inhibitor of tumor cell invasion produced by the actinomycete of the genus Nonomuraea. In order to find more potent anti-invasive agents and study the structure-activity relationships, a series of 19 brartemicin analogs were prepared via two synthetic routes from alpha,alpha-D-trehalose and evaluated for their anti-invasive activities. Compound 4f, 6,6'-bis(2,3-dimethoxybenzoyl)-alpha,alpha-D-trehalose, was more potent than the natural brartemicin. It inhibited the invasion of murine colon 26-L5, colon carcinoma SW620, melanoma B16-BL6 and breast MDA-MB-231 cells with IC50 values of 0.15, 2.35, 4.12 and 2.61 mu M, respectively. Analog 4p, 6,6'-bis(3,4-dimethoxycinnamoyl)-alpha,alpha-D-trehalose, was as potent as brartemicin against invasion of murine colon 26-L5 carcinoma cells in vitro. The structure-activity relationships of these novel trehalose-based compounds were summarized.