Discovery of antitumor diterpenoids from Casearia graveolens targeting VEGFR-2 to inhibit angiogenesis  

作　　者：WANG Sibei LIU Yuhui LIANG Yue XI Yaru ZHAI Yupeng LEE Dongho XU Jing GUO Yuanqiang 

机构地区：[1]State Key Laboratory of Medicinal Chemical Biology,College of Pharmacy,and Tianjin Key Laboratory of Molecular Drug Research,Nankai University,Tianjin 300350,China [2]State Key Laboratory of Functions and Applications of Medicinal Plants,Guizhou Medical University,Guiyang 550014,China [3]Department of Plant Biotechnology,College of Life Sciences and Biotechnology,Korea University,Seoul 02841,South Korea

出　　处：《Chinese Journal of Natural Medicines》2024年第9期842-853,共12页中国天然药物（英文版）

基　　金：supported by the National Natural Science Foundation of China(No.22077067);the Project of State Key Laboratory of Functions and Applications of Medicinal Plants,Guizhou Medical University[No.QJJ(2022)422];the 111 Project(No.B20016)。

摘　　要：Eight novel clerodane diterpenoids(1-8)were isolated from the twigs of Casearia graveolens.Their structures were elucidated through comprehensive nuclear magnetic resonance(NMR),high-resolution electrospray ionization mass spectrometry(HRESI-MS),and electronic circular dichroism(ECD)analyses.In addition to structural determination,surface plasmon resonance(SPR)assays were conducted to investigate molecular interactions,revealing that compound 8 exhibited high affinity for vascular endothelial growth factor receptor 2(VEGFR2),a key regulator of tumor angiogenesis.Subsequent in vivo experiments demonstrated that compound 8 effectively inhibited angiogenesis and displayed significant antitumor activity by suppressing tumor proliferation and metastasis in zebrafish xenograft models.These findings suggest that compound 8 holds promise as an anticancer lead compound targeting VEGFR-2 to obstruct tumor angiogenesis.

关 键 词：Clerodane diterpenoids Casearia graveolens Surface plasmon resonance Vascular endothelial growth factor receptor 2 Antitumor activity ZEBRAFISH 

分 类 号：R284[医药卫生—中药学] R965[医药卫生—中医学]