Chen Zeping, Mou Ying, Zhong Hao, Xu Jiekun, Zhang Xiaoqi, Li Guoqiang, He Jun, Zhang Weiku, Huang Weihuan, Tian Haiyan
Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou, 510632, People's Republic of China.
Key Laboratory of Regenerative Medicine, Ministry of Education, Jinan University, Guangzhou, 510632, People's Republic of China.
Phytochemistry. 2022 Nov;203:113399. doi: 10.1016/j.phytochem.2022.113399. Epub 2022 Aug 24.
Fourteen undescribed cassaine diterpenoids along with nine known ones were isolated from the seeds of Erythrophleum fordii Oliv. (Leguminosae). In addition, subsequent structural modification yielded ten derivatives. Their chemical structures were established by extensive spectroscopic methods and acid hydrolysis. All the diterpenoids were screened for their antiangiogenic activity using the human umbilical vein endothelial cell (HUVEC) model. Five compounds were active, of which three possessed excellent activity as their effect was better than that of the positive control (SU5416). The structure-activity relationship analysis revealed that the side chain at C-13 was the key part affecting the inhibitory effect. Further study demonstrated that 3β-hydroxynorerythrosuamine-3-O-β-D-glucopyranoside and the formate of 3β-hydroxynorerythrosuamine-3-O-β-D-glucopyranoside significantly inhibited a series of angiogenic processes including proliferation, migration and capillary-like structure formation of endothelial cells. These findings may provide a new type of antiangiogenic agent for future cancer drug development.
从苏木科植物山苏木（Erythrophleum fordii Oliv.）的种子中分离得到了14个未被描述的长春花二萜类化合物以及9个已知化合物。此外，后续的结构修饰得到了10个衍生物。通过广泛的光谱方法和酸水解确定了它们的化学结构。使用人脐静脉内皮细胞（HUVEC）模型对所有二萜类化合物进行了抗血管生成活性筛选。有5种化合物具有活性，其中3种表现出优异的活性，其效果优于阳性对照（SU5416）。构效关系分析表明，C-13位的侧链是影响抑制作用的关键部分。进一步研究表明，3β-羟基去甲赤藓胺-3-O-β-D-吡喃葡萄糖苷和3β-羟基去甲赤藓胺-3-O-β-D-吡喃葡萄糖苷的甲酸盐显著抑制了包括内皮细胞增殖、迁移和毛细血管样结构形成在内的一系列血管生成过程。这些发现可能为未来的癌症药物开发提供一种新型抗血管生成剂。
