Ruthenium anticancer compounds: myths and realities of the emerging metal-based drugs

Dalton Trans. 2011 Aug 21;40(31):7817-23. doi: 10.1039/c0dt01816c. Epub 2011 Jun 1.

Abstract

Ruthenium anticancer drugs have attracted an increasing interest in the last 20 years and two of them have entered clinical trials. Compared to platinum drugs, the complexes based on ruthenium are often identified as less toxic and capable of overcoming the resistance induced by platinum drugs in cancer cells. These activities were attributed to the transportation to tumour cells by transferrin and to the selective activation to more reactive species by the reducing environment of solid tumours as compared to healthy tissues. Ruthenium anticancer drugs have been almost always designed to mimic platinum drugs, particularly for targeting DNA. Indeed, none of the above properties has never been clearly demonstrated even for the ruthenium drugs that entered clinical trials. The suggestion for the future is to change the perspective when designing new chemical entities, abandoning the philosophy that guided the actual panel of ruthenium drugs and to look further into the fine mechanism by which the most relevant ruthenium complexes available kill the target tumour cells, then focusing on targets selective of tumour cells and responsible for cell growth and malignancy.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / therapeutic use*
  • Dimethyl Sulfoxide / analogs & derivatives
  • Dimethyl Sulfoxide / pharmacokinetics
  • Drug Delivery Systems
  • Drug Design*
  • Humans
  • Indazoles / pharmacokinetics
  • Neoplasms / drug therapy*
  • Organometallic Compounds / chemistry*
  • Organometallic Compounds / pharmacokinetics
  • Organometallic Compounds / therapeutic use
  • Ruthenium Compounds / chemistry
  • Ruthenium Compounds / pharmacokinetics
  • Ruthenium Compounds / therapeutic use*

Substances

  • Antineoplastic Agents
  • Indazoles
  • Organometallic Compounds
  • Ruthenium Compounds
  • imidazolium-bis(imidazole)dimethylsulfoxideimidazotetrachlororuthenate(III)
  • indazolium trans-(tetrachlorobis(1H-indazole)ruthenate (III))
  • Dimethyl Sulfoxide