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来自[具体来源未提及]的强心苷及其细胞毒性活性。

Cardiac glycosides from and their cytotoxic activities.

作者信息

Yang Hong-Ying, Chen Ya-Xiong, Luo Shangwen, He Yi-Lin, Feng Wei-Jiao, Sun Yue, Chen Jian-Jun, Gao Kun

机构信息

State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University 222 Tianshui South Road, Chengguan District Lanzhou Gansu 730000 People's Republic of China

Key Laboratory of Space Radiobiology of Gansu Province & CAS Key Laboratory of Heavy Ion Radiation Biology and Medicine, Institute of Modern Physics, Chinese Academy of Sciences Lanzhou 730000 Gansu China.

出版信息

RSC Adv. 2022 Aug 16;12(36):23240-23251. doi: 10.1039/d2ra04464a.

DOI:10.1039/d2ra04464a
PMID:36090389
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9380703/
Abstract

Cardiac glycosides (CGs) are good candidates as drug leads in the treatment of cancer because of their structural diversities and potent biological activities. In this study, fifteen CGs including three new ones (1-3) were isolated from Ehrh. Their structures were elucidated by HRESIMS, NMR spectroscopic methods, including homonuclear and heteronuclear coupling constant analysis, and acid-catalyzed hydrolysis and derivatization analysis of the sugar chain. The cytotoxic activities of these CGs were evaluated against three human cancer cell lines (A549, HeLa and MCF-7 cell lines), and all of them showed strong activities at nanomolar scale. The flow cytometric analysis indicated that compound 1 induced cell cycle arrest in the G2/M phase. Transcriptome analysis revealed a panel of possible targets for compound 1. RT-PCR and western blot experiments showed that 1 significantly inhibited the expression of vasohibin-2 (VASH2). Moreover, compound 1 restrained angiogenesis in a concentration-dependent manner in the chick embryo chorioallantoic membrane (CAM) model.

摘要

强心苷（CGs）因其结构多样性和强大的生物活性，是治疗癌症的良好药物先导化合物候选物。在本研究中，从Ehrh.中分离出15种强心苷，包括3种新的强心苷（1 - 3）。通过高分辨电喷雾电离质谱（HRESIMS）、核磁共振光谱方法（包括同核和异核耦合常数分析）以及糖链的酸催化水解和衍生化分析来阐明它们的结构。评估了这些强心苷对三种人类癌细胞系（A549、HeLa和MCF - 7细胞系）的细胞毒性活性，所有这些强心苷在纳摩尔浓度下均表现出强大的活性。流式细胞术分析表明化合物1诱导细胞周期停滞在G2/M期。转录组分析揭示了化合物1的一组可能靶点。逆转录 - 聚合酶链反应（RT - PCR）和蛋白质免疫印迹实验表明，化合物1显著抑制血管抑制素 - 2（VASH2）的表达。此外，在鸡胚绒毛尿囊膜（CAM）模型中，化合物1以浓度依赖的方式抑制血管生成。

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