PUBLICATION
Discovery of Arene Ruthenium(II) Complexes as Potential VEGF Inhibitors for Glioblastoma Metastasis Suppression
- Authors
- Yuan, C., Zhu, C., Lv, Q., Shi, J., Wang, J., Gao, S., Qian, J., Chen, Y., Wu, Q., Mei, W.
- ID
- ZDB-PUB-241022-1
- Date
- 2024
- Source
- Journal of medicinal chemistry 67(21): 18724-18740 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- DNA Damage/drug effects
- Structure-Activity Relationship
- Zebrafish*
- Coordination Complexes*/chemical synthesis
- Coordination Complexes*/chemistry
- Coordination Complexes*/pharmacology
- Coordination Complexes*/therapeutic use
- Antineoplastic Agents*/chemical synthesis
- Antineoplastic Agents*/chemistry
- Antineoplastic Agents*/pharmacology
- Antineoplastic Agents*/therapeutic use
- Glioblastoma*/drug therapy
- Glioblastoma*/metabolism
- Glioblastoma*/pathology
- Autophagy/drug effects
- Drug Discovery
- Cell Proliferation*/drug effects
- Humans
- G-Quadruplexes/drug effects
- Animals
- Vascular Endothelial Growth Factor A*/antagonists & inhibitors
- Vascular Endothelial Growth Factor A*/metabolism
- Cell Line, Tumor
- Ruthenium*/chemistry
- Ruthenium*/pharmacology
- PubMed
- 39433480 Full text @ J. Med. Chem.
Citation
Yuan, C., Zhu, C., Lv, Q., Shi, J., Wang, J., Gao, S., Qian, J., Chen, Y., Wu, Q., Mei, W. (2024) Discovery of Arene Ruthenium(II) Complexes as Potential VEGF Inhibitors for Glioblastoma Metastasis Suppression. Journal of medicinal chemistry. 67(21):18724-18740.
Abstract
Developing drugs for treating glioblastoma has been a significant challenge. Herein, a series of arene ruthenium(II) complexes have been synthesized and investigated as potential candidates to suppress the proliferation and metastasis of glioblastoma. It is found that para-substituent-modified molecules, especially 6, exhibit higher antitumor activity than ortho-substituents. Further studies show that 6 can trigger tumor cell autophagy by regulating the PI3K/AKT/mTOR pathway. Moreover, it is also found that 6 can induce DNA damage in glioblastoma cells through binding and stabilizing VEGF G-quadruplex DNA. Furthermore, it is confirmed that 6 can inhibit the proliferation and metastasis of U87-MG glioblastoma cell in situ xenograft in the zebrafish model. Hence, arene ruthenium(II) complexes can be developed as promising therapeutic agents for glioblastoma treatment in the future.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping