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

Chanling Yuan,Chunguang Zhu,Qingshuang Lv,Jiahui Shi,Jiacheng Wang,Shiqi Gao,Jiayi Qian,Yanhua Chen,Qiong Wu,Wenjie Mei

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.