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从[植物名称]地下部分分离出的16种未描述甾体糖苷的结构解析及其对小细胞肺癌细胞的凋亡诱导活性

Structure Elucidation of 16 Undescribed Steroidal Glycosides from the Underground Parts of and Apoptosis-Inducing Activity in Small-Cell Lung Cancer Cell.

作者信息

Takahashi Naoki, Iguchi Tomoki, Nagamine Anju, Shirai Remina, Nagata Akihiro, Yamauchi Junji, Mimaki Yoshihiro

机构信息

Department of Medicinal Pharmacognosy, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1, Horinouchi, Hachioji, Tokyo 192-0392, Japan.

Laboratory of Molecular Neurology, School of Life Science, Tokyo University of Pharmacy and Life Sciences, 1432-1, Horinouchi, Hachioji, Tokyo 192-0392, Japan.

出版信息

ACS Omega. 2023 Jan 6;8(2):2808-2830. doi: 10.1021/acsomega.2c07766. eCollection 2023 Jan 17.

Abstract

To explore new candidates for anticancer agents from natural products, the underground parts of , commonly used as an ornamental plant, were investigated phytochemically. As a result, 16 undescribed steroidal glycosides (-) were obtained, and their structures were determined mainly by NMR spectroscopic analysis and chemical transformations. The cytotoxic activities of the isolated compounds (-) against SBC-3 human small-cell lung cancer cells, A549 human adenocarcinoma cells, and HL-60 human promyelocytic leukemia cells were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2-tetrazolium bromide (MTT) assay. Compound , a bisdesmosidic furostanol glycoside, and , a bisdesmosidic spirostanol glycoside, were cytotoxic to all three cell lines with IC values ranging from 1.2 to 13 μM. As exhibited the most potent cytotoxicity against SBC-3 cells among the isolated compounds, its apoptosis-inducing activity toward SBC-3 cells was examined. Compound arrested SBC-3 cells at the G/M phase of the cell cycle and effectively induced apoptosis via an intrinsic pathway accompanied by the dissipation of membrane potential and morphological changes in mitochondria.

摘要

为了从天然产物中探索新型抗癌药物候选物,对通常用作观赏植物的[植物名称]的地下部分进行了植物化学研究。结果,获得了16种未描述的甾体糖苷(-),其结构主要通过核磁共振光谱分析和化学转化确定。使用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基-2-四氮唑溴盐(MTT)法评估了分离得到的化合物(-)对SBC-3人小细胞肺癌细胞、A549人腺癌细胞和HL-60人早幼粒细胞白血病细胞的细胞毒性活性。化合物[具体化合物名称1],一种双去氧糖呋甾烷醇糖苷,和[具体化合物名称2],一种双去氧糖螺甾烷醇糖苷,对所有三种细胞系均具有细胞毒性,IC值范围为1.2至13μM。由于[具体化合物名称1]在分离得到的化合物中对SBC-3细胞表现出最强的细胞毒性,因此检测了其对SBC-3细胞的凋亡诱导活性。化合物[具体化合物名称1]使SBC-3细胞停滞在细胞周期的G/M期,并通过内在途径有效诱导凋亡,伴随着膜电位的消散和线粒体的形态变化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92cb/9851033/6eaced15f97f/ao2c07766_0002.jpg

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