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

Despite the clinical success of Pt anti-cancer drugs, metal-based drugs are slow to enter the clinic, due to their coordination chemistry and typically short lifetimes in biological environments. We propose that this can be turned into advantage for direct injections into the tumor, which will allow use of highly cytotoxic drugs. The release of their less toxic decomposition products into the blood will lead to reduced systemic toxicity and can even have beneficial effect, such as the neurostimulatory activity of vanadium.  In particular, a ternary V(V) complex, 1 ([VOL1L2], where L1 is N-(salicylideneaminato)-N-(2-hydroxyethyl)ethane-1,2-diamine, and L2 is 3,5-di-tert-butylcatechol), 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. Complex 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 favour further development of 1 for brain cancer treatment by intratumoral injections.