A Short‐Lived but Highly Cytotoxic Vanadium(V) Complex as a Potential Drug Lead for Brain Cancer Treatment by Intratumoral Injections

The chemistry and short lifetimes of metal‐based anti‐cancer drugs can be turned into an advantage for direct injections into tumors, which then allow the use of highly cytotoxic drugs. The release of their less toxic decomposition products into the blood will lead to decreased toxicity and can even have beneficial effects. We present a ternary VV complex, 1 ([VOL1L2], where L1 is N‐(salicylideneaminato)‐N′‐(2‐hydroxyethyl)ethane‐1,2‐diamine and L2 is 3,5‐di‐tert‐butylcatechol), which enters cells intact to induce high cytotoxicity in a range of human cancer cells, including T98g (glioma multiforme), while its decomposition products in cell culture medium were ≈8‐fold less toxic. 1 was 12‐fold more toxic than cisplatin in T98g cells and 6‐fold more toxic in T98g cells than in a non‐cancer human cell line, HFF‐1. Its high toxicity in T98g cells was retained in the presence of physiological concentrations of the two main metal‐binding serum proteins, albumin and transferrin. These properties favor further development of 1 for brain cancer treatment by intratumoral injections. V for Vanadium: A drastic decrease in cytotoxicity of a mixed‐ligand VV complex 1 after its decomposition in biological media can be employed in intratumoral injections, particularly for brain cancer. The release of relatively non‐toxic V decomposition products into the blood is expected to reduce the side effects and may also be beneficial due to the known neurostimulatory properties of V.