Wuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China.
Wuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China.
Bioorg Chem. 2021 May;110:104809. doi: 10.1016/j.bioorg.2021.104809. Epub 2021 Mar 12.
Seven undescribed withanolides (1-7) and six artificial withanolides (8-13), along with 20 known compounds (14-33) were isolated from the aerial parts of Tubocapsicum anomalum. Their structures were confirmed by comprehensive spectroscopic analyses. The absolute configuration of compound 1 was 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 compound 24 (tubocapsanolide A) exhibited the highest activities against the MDA-MB-231 cells with an IC value of 1.89 ± 1.03 μM. Further studies showed that 24 exhibited significant damage to mitochondria in MDA-MB-231 cells, including excess reactive oxygen species, decreased mitochondrial membrane potential, and apoptosis initiation. In addition, compound 24 also inhibited cell migration. These findings show that tubocapsanolide A may be a promising molecule for triple-negative breast cancer treatment and merit further evaluation.
从 Tubocapsicum anomalum 的地上部分分离得到了 7 个未描述的醉茄内酯（1-7）和 6 个人工醉茄内酯（8-13），以及 20 个已知化合物（14-33）。通过综合光谱分析确定了它们的结构。通过单晶 X 射线晶体学确定了化合物 1 的绝对构型。所有分离物均针对五种人肿瘤细胞系（Hep3B、MDA-MB-231、SW480、HCT116 和 A549）的抗增殖活性进行了评估，其中化合物 24（tubocapsanolide A）对 MDA-MB-231 细胞表现出最高的活性，IC 值为 1.89±1.03μM。进一步的研究表明，24 在 MDA-MB-231 细胞中对线粒体造成了显著的损伤，包括过量的活性氧、线粒体膜电位降低和凋亡起始。此外，化合物 24 还抑制细胞迁移。这些发现表明 tubocapsanolide A 可能是治疗三阴性乳腺癌的有前途的分子，值得进一步评估。
