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

Angew Chem Int Ed Engl. 2020 Sep 7;59(37):15834-15838. doi: 10.1002/anie.202005458. Epub 2020 Aug 11.

Abstract

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 ([VOL1 L2 ], 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.

Keywords: anti-cancer treatment; intratumoral injection; neuroprotection; non-innocent mixed ligands; vanadium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / therapeutic use
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Coordination Complexes / chemistry*
  • Coordination Complexes / therapeutic use
  • Culture Media
  • Drug Discovery
  • Drug Screening Assays, Antitumor
  • Humans
  • Proton Magnetic Resonance Spectroscopy
  • Vanadium Compounds / chemistry*
  • Vanadium Compounds / therapeutic use

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • Culture Media
  • Vanadium Compounds