白英中三个未被报道的甾体糖苷生物碱及其抗肿瘤活性

doi:10.5246/jcps.2022.03.017

中国药学(英文版) ›› 2022, Vol. 31 ›› Issue (3): 192-201.DOI: 10.5246/jcps.2022.03.017

白英中三个未被报道的甾体糖苷生物碱及其抗肿瘤活性

刘良裕¹, 杨宇珂¹, 杜肖²^,³^,^*(), 吴桐¹, 王建农¹^,^*()

1. 中国中医科学院西苑医院基础医学研究所中药药理北京市重点实验室, 北京 100091
2. 华润三九医药股份有限公司, 广东深圳 518110
3. 中国中医科学院博士后流动站, 北京 100700

收稿日期:2021-09-14 修回日期:2021-10-02 接受日期:2021-11-17 出版日期:2022-03-31 发布日期:2022-03-31
通讯作者: 杜肖, 王建农
作者简介:
+ Tel.: +86-13011239677, E-mail: duxiao9@999.com.cn
+ Tel.: +86-10-62835620, E-mail: wangjiannong2008@sina.com
基金资助:
National Natural Science Foundation of China (Grant No. 81872989).

Three previously undescribed steroidal glycoalkaloids from Solanum lyratum and their anti-tumor activities

Liangyu Liu¹, Yuke Yang¹, Xiao Du²^,³^,^*(), Tong Wu¹, Jiannong Wang¹^,^*()

1 Key Laboratory of Chinese Medicine Pharmacology, Institute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, 100091 Beijing, China
2 China Resources Sanjiu Medical & Pharmaceutical Co. Ltd., Shenzhen 518110, China
3 Postdoctoral Mobile Research Station of China Academy of Chinese Medical Sciences, Beijing 100700, China

Received:2021-09-14 Revised:2021-10-02 Accepted:2021-11-17 Online:2022-03-31 Published:2022-03-31
Contact: Xiao Du, Jiannong Wang

摘要/Abstract

摘要：

本研究从白英中分离得到3个未被报道的甾体糖苷生物碱(化合物1–3), 借助综合光谱分析, 阐明了它们的结构。通过MTT和划痕愈合实验分别评价其抗肿瘤血管生成和转移活性, 为更好的模拟体内肿瘤环境, 将人非小细胞肺癌细胞株A549与人脐静脉内皮细胞共培养获得肿瘤血管内皮细胞(TdECs)模型, 用化合物1–3分别处理TdECs。结果显示, 尽管它们对TdECs的细胞毒活性相对较弱, 但在25 μM时均能明显抑制TdECs的迁移。这些结果表明, 化合物1–3并不是通过影响肿瘤血管内皮细胞的增殖直接作用于血管生成, 而是通过抑制肿瘤细胞的转移发挥抗肿瘤活性。

关键词: 白英, 甾体糖苷生物碱, 抗肿瘤, 转移, 血管生成

Abstract:

In the present study, three previously undescribed steroidal glycoalkaloids (compounds 1–3) were isolated from Solanum lyratum. Their structures were elucidated based on comprehensive spectroscopic data. Their anti-angiogenesis and anti-metastatic activities were evaluated by MTT and wound-healing assays, respectively. Tumor-derived vascular endothelial cells (TdECs), obtained by co-culture of A549 and human umbilical vein endothelial cells (HUVECs), were treated with compounds 1–3. Results showed that compounds 1–3 significantly inhibited the migration of TdECs at 25 μM despite the weak cytotoxic activities, which indicated that the compounds exerted anti-tumor activities by inhibiting metastasis, rather than directly inhibiting the proliferation of TdECs.

Key words: Solanum lyratum, Steroidal glycoalkaloids, Anti-tumor, Metastasis, Angiogenesis

Supporting:

刘良裕, 杨宇珂, 杜肖, 吴桐, 王建农. 白英中三个未被报道的甾体糖苷生物碱及其抗肿瘤活性[J]. 中国药学(英文版), 2022, 31(3): 192-201.

Liangyu Liu, Yuke Yang, Xiao Du, Tong Wu, Jiannong Wang. Three previously undescribed steroidal glycoalkaloids from Solanum lyratum and their anti-tumor activities[J]. Journal of Chinese Pharmaceutical Sciences, 2022, 31(3): 192-201.

图/表 6

Table 1. 1H NMR (600 MHz) and 13C NMR (150 MHz) data for compounds 1–3 in methanol-d4 (δ in ppm, J in Hz).

Figure 1. Structures of compounds 1–3.

Figure 2. Key 1H-1H COSY and HMBC correlations of compounds 1–3.

Figure 3. NOESY correlations of compounds 1 and 3.

Figure 4. MTT results of compounds 1–3 on TdECs.

Figure 5. Compounds 1–3 inhibit the migration of TdECs in wound-healing assay.

参考文献 21

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白英中三个未被报道的甾体糖苷生物碱及其抗肿瘤活性

Three previously undescribed steroidal glycoalkaloids from Solanum lyratum and their anti-tumor activities

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