Ruthenium antimetastatic agents

Curr Top Med Chem. 2004;4(15):1525-35. doi: 10.2174/1568026043387421.

Abstract

NAMI-A, i. e. (imH)[trans-RuCl(4)(dmso-S)(im)] (im = imidazole, dmso = dimethylsulfoxide), is a Ru(III) complex that, after extensive preclinical investigations that evidenced its remarkable and specific activity against metastases, has recently and successfully completed a Phase I trial (first ruthenium complex ever to reach clinical testing). This review article, after a brief summary of the main chemical and pharmacological aspects of NAMI-A, focuses on the development of new classes of ruthenium complexes originated from the NAMI-A frame. In particular, the chemical and biological features of the following classes of compounds will be treated: i) NAMI-A-type complexes, derived from NAMI-A by changing the nature of the N-ligand, ii) dinuclear NAMI-A-type compounds containing heterocyclic bridging N-N ligands, iii) new Ru-dmso nitrosyls broadly derived from NAMI-A-type complexes. Several of these new compounds were found to have antimetastatic activity comparable to, or even better than, NAMI-A; however, the nature of the target(s) responsible for the antimetastatic activity remains unclear. Common to any type of NAMI-A-type compound, both monomeric and dimeric, cell cytotoxicity (which is generally very low) is not sufficient to explain their potent and peculiar antitumor activity. All active NAMI-A-type compounds share the capacity to modify important parameters of metastasis such as tumor invasion, matrix metallo proteinases activity and cell cycle progression.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents* / chemical synthesis
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Dimethyl Sulfoxide* / analogs & derivatives*
  • Dimethyl Sulfoxide* / chemical synthesis
  • Dimethyl Sulfoxide* / chemistry
  • Dimethyl Sulfoxide* / pharmacology
  • Humans
  • Ligands
  • Molecular Conformation
  • Neoplasm Metastasis / prevention & control*
  • Organometallic Compounds* / chemical synthesis
  • Organometallic Compounds* / chemistry
  • Organometallic Compounds* / pharmacology
  • Ruthenium / chemistry*
  • Ruthenium Compounds

Substances

  • Antineoplastic Agents
  • Ligands
  • Organometallic Compounds
  • Ruthenium Compounds
  • imidazolium-bis(imidazole)dimethylsulfoxideimidazotetrachlororuthenate(III)
  • Ruthenium
  • Dimethyl Sulfoxide