Discovery of Arene Ruthenium(II) Complexes as Potential VEGF Inhibitors for Glioblastoma Metastasis Suppression

  • J Med Chem. 2024 Nov 14;67(21):18724-18740. doi: 10.1021/acs.jmedchem.4c00797.
Chanling Yuan  1 ,  Chunguang Zhu  1 ,  Qingshuang Lv  1 ,  Jiahui Shi  1 ,  Jiacheng Wang  1 ,  Shiqi Gao  1 ,  Jiayi Qian  1 ,  Yanhua Chen  1 ,  Qiong Wu  2 ,  Wenjie Mei  1
Affiliations
  • 1. School of Pharmacy, Guangdong Province Engineering and Technology Centre for Molecular Probe and Biomedicine Imaging, Guangdong Pharmaceutical University, Guangzhou 510006, China.
  • 2. Institute of Biological and Medical Engineering, Guangdong Academy of Sciences, Guangzhou 530316, China.
PMID: 39433480 DOI: 10.1021/acs.jmedchem.4c00797
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.

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