PUBLICATION
Discovery of antitumor diterpenoids from Casearia graveolens targeting VEGFR-2 to inhibit angiogenesis
- Authors
- Wang, S., Liu, Y., Liang, Y., Xi, Y., Zhai, Y., Lee, D., Xu, J., Guo, Y.
- ID
- ZDB-PUB-240927-1
- Date
- 2024
- Source
- Chinese Journal of Natural Medicines 22: 842853842-853 (Journal)
- Registered Authors
- Keywords
- Antitumor activity, Casearia graveolens, Clerodane diterpenoids, Surface plasmon resonance, Vascular endothelial growth factor receptor 2, Zebrafish
- MeSH Terms
-
- Antineoplastic Agents, Phytogenic/chemistry
- Antineoplastic Agents, Phytogenic/pharmacology
- Molecular Structure
- Humans
- Animals
- Zebrafish*
- Casearia*/chemistry
- Diterpenes/chemistry
- Diterpenes/isolation & purification
- Diterpenes/pharmacology
- Angiogenesis Inhibitors*/chemistry
- Angiogenesis Inhibitors*/isolation & purification
- Angiogenesis Inhibitors*/pharmacology
- Neovascularization, Pathologic/drug therapy
- Cell Line, Tumor
- Vascular Endothelial Growth Factor Receptor-2*/antagonists & inhibitors
- Vascular Endothelial Growth Factor Receptor-2*/metabolism
- Diterpenes, Clerodane/chemistry
- Diterpenes, Clerodane/pharmacology
- Angiogenesis
- PubMed
- 39326978 Full text @ Chin. J. Nat. Med.
Citation
Wang, S., Liu, Y., Liang, Y., Xi, Y., Zhai, Y., Lee, D., Xu, J., Guo, Y. (2024) Discovery of antitumor diterpenoids from Casearia graveolens targeting VEGFR-2 to inhibit angiogenesis. Chinese Journal of Natural Medicines. 22:842853842-853.
Abstract
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 (HR-ESI-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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping