Discovery of\nArene Ruthenium(II) Complexes as Potential\nVEGF Inhibitors for Glioblastoma Metastasis Suppression

Developing\ndrugs for treating glioblastoma has been a\nsignificant\nchallenge. Herein, a series of arene ruthenium(II) complexes have\nbeen synthesized and investigated as potential candidates to suppress\nthe proliferation and metastasis of glioblastoma. It is found that\npara-substituent-modified molecules, especially <b>6</b>, exhibit\nhigher antitumor activity than ortho-substituents. Further studies\nshow that <b>6</b> can trigger tumor cell autophagy by regulating\nthe PI3K/AKT/mTOR pathway. Moreover, it is also found that <b>6</b> can induce DNA damage in glioblastoma cells through binding and\nstabilizing VEGF G-quadruplex DNA. Furthermore, it is confirmed that <b>6</b> can inhibit the proliferation and metastasis of U87-MG glioblastoma\ncell in situ xenograft in the zebrafish model. Hence, arene ruthenium(II)\ncomplexes can be developed as promising therapeutic agents for glioblastoma\ntreatment in the future.