Semisynthesis and Non-Small-Cell Lung Cancer Cytotoxicity Evaluation of Germacrane-Type Sesquiterpene Lactones from Elephantopus scaber
Semisynthesis and Non-Small-Cell Lung Cancer Cytotoxicity Evaluation of Germacrane-Type Sesquiterpene Lactones from Elephantopus scaber
复制标题
象斑草中香叶兰型倍半萜内酯的半合成和非小细胞肺癌细胞毒性评价。
DOI：
10.1021/acs.jnatprod.1c00936
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发表时间：
2022-02-25
影响因子：
5.1
通讯作者：
Song, Shao-Jiang
中科院分区：
文献类型：
--
作者：
Ren, Hui;Zhang, Yang-Yang;Song, Shao-Jiang
以赤霉醇C为原料，经标准化学转化制得两个系列的吉马克兰型倍半萜内酯。筛选了它们对非小细胞肺癌细胞的抑制活性，并初步建立了构效关系。其中，单体类似物1U和二聚类似物3D具有较强的抗非小细胞肺癌细胞毒活性，对A549细胞的IC50值分别为4.3和0.7mU，均高于顺铂和标准倍半萜内酯、巴马烯内酯和马钱子素。进一步的研究表明，化合物1U和3D通过激活线粒体通路诱导A549细胞发生G2/M期停滞和诱导细胞凋亡。总之，所获得的结果表明，化合物1U和3D是很有希望的抗非小细胞肺癌先导化合物。
Two series of germacrane-type sesquiterpene lactones were produced by semisynthetic modulation of scaberol C, which was prepared by a standard chemical transformation from an Elephantopus scaber extract. Their inhibition activities against non-small-cell lung cancer cells were screened, and preliminary structure-activity relationships were also established. Among them, monomeric analog 1u and dimeric analog 3d exhibited superior anti-non-small-cell lung cancer cytotoxic potencies with IC50 values of 4.3 and 0.7 mu M against A549 cells, respectively, and were more active than cisplatin and the standard sesquiterpene lactones, parthenolide and scabertopin. Further studies revealed that compounds 1u and 3d cause G2/M phase arrest and induce apoptosis through the activation of mitochondrial pathways in A549 cells. Collectively, the results obtained suggest that compounds 1u and 3d are promising anti-non-small-cell lung cancer lead compounds.