Dehydroleucodine, a Sesquiterpene Lactone from Gynoxys verrucosa, Demonstrates Cytotoxic Activity against Human Leukemia Cells
Dehydroleucodine, a Sesquiterpene Lactone from Gynoxys verrucosa, Demonstrates Cytotoxic Activity against Human Leukemia Cells
复制标题
DOI：
10.1021/acs.jnatprod.5b00383
复制
发表时间：
2016-04-01
影响因子：
5.1
通讯作者：
Compadre, Cesar M.
中科院分区：
文献类型：
--
作者：
Ordonez, Paola E.;Sharma, Krishan K.;Compadre, Cesar M.
从厄瓜多尔南部的传统药用植物--多疣Gynoxys verrucosa中分离得到了倍半萜内酯脱氢亮甲素（1）和亮甲素（2）。这些化合物的活性测定对八个急性髓性白血病（AML）细胞系，并与它们的活性对正常外周血单核细胞进行比较。化合物1显示出对测试细胞系的细胞毒活性，LD 50值在5.0和18.9 μ M之间。化合物2对所有测试的细胞系均无活性，表明内酯环中的环外亚甲基是细胞毒性活性所需的。重要的是，化合物1对正常血细胞的毒性比对AML细胞系的毒性小，并且对来自5名患者的人AML细胞样品有活性，平均LD 50为9.4 μ M。机理分析表明，化合物1具有与孤雌菊类似的作用机制（3）。虽然这些化合物具有显着的结构差异，但它们的亲脂性表面特征显示出惊人的相似性。
The sesquiterpene lactones dehydroleucodine (1) and leucodine (2) were isolated from Gynoxys verrucosa, a species used in traditional medicine in southern Ecuador. The activity of these compounds was determined against eight acute myeloid leukemia (AML) cell lines and compared with their activity against normal peripheral blood mononuclear cells. Compound 1 showed cytotoxic activity against the tested cell lines, with LD50 values between 5.0 and 18.9 mu M. Compound 2 was inactive against all of the tested cell lines, demonstrating that the exocyclic methylene in the lactone ring is required for cytotoxic activity. Importantly, compound 1 induced less toxicity to normal blood cells than to AML cell lines and was active against human AML cell samples from five patients, with an average LD50 of 9.4 mu M. Mechanistic assays suggest that compound 1 has a similar mechanism of action to parthenolide (3). Although these compounds have significant structural differences, their lipophilic surface signatures show striking similarities.