Withanolides isolated from Tubocapsicum anomalum and their antiproliferative activity
Withanolides isolated from Tubocapsicum anomalum and their antiproliferative activity
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从 Tubocapsicum anomalum 中分离的睡茄内酯及其抗增殖活性
DOI：
10.1016/j.bioorg.2021.104809
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发表时间：
2021
影响因子：
5.1
通讯作者：
Chen Li-Xia
中科院分区：
文献类型：
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作者：
Xiang Ke;Li Chen;Li Ming-Xue;Song Zhuo-Rui;Ma Xiao-Xin;Sun De-Juan;Li Hua;Chen Li-Xia
从异形管的地上部分分离得到7个未见文献报道的双环花内酯(1-7)和6个人工双环花内酯(8-13)以及20个已知化合物(14-33)。它们的结构经全面的波谱分析确证。用单晶X射线结晶学确定了化合物1的绝对构型。所有分离株对5种人肿瘤细胞系(Hep3B、MDAMB-231、SW480、HCT116和A549)的抗增殖作用进行了评估，其中化合物24(Tubocapsanolide A)对mda-MB-231细胞的抑制作用最强，IC50值为1.89±1.03μM。进一步的研究表明，24对mda-MB-231细胞的线粒体具有明显的损伤作用，包括活性氧含量增加，线粒体膜电位降低，启动细胞凋亡。此外，化合物24还抑制细胞迁移。这些发现表明，管香内酯A可能是一个有希望的分子，用于三阴性乳腺癌的治疗，值得进一步评估。
Seven undescribed withanolides (1–7) and six artificial withanolides (8–13), along with 20 known compounds (14–33) were isolated from the aerial parts ofTubocapsicum anomalum. Their structures were confirmed by comprehensive spectroscopic analyses. The absolute configuration of compound1was defined by single-crystal X-ray crystallography. All isolates were evaluated for their antiproliferative effects against five human tumor cell lines (Hep3B, MDA-MB-231, SW480, HCT116 and A549), among which compound24(tubocapsanolide A) exhibited the highest activities against the MDA-MB-231 cells with an IC50value of 1.89 ± 1.03 μM. Further studies showed that24exhibited significant damage to mitochondria in MDA-MB-231 cells, including excess reactive oxygen species, decreased mitochondrial membrane potential, and apoptosis initiation. In addition, compound24also inhibited cell migration. These findings show that tubocapsanolide A may be a promising molecule for triple-negative breast cancer treatment and merit further evaluation.