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...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.展开更多
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)。
文摘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.
