Ruthenium Antimetastatic Agents

Author(s): Enzo Alessio, Giovanni Mestroni, Alberta Bergamo, Gianni Sava.

Journal Name: Current Topics in Medicinal Chemistry

Volume 4 , Issue 15 , 2004

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Abstract:

NAMI-A, i. e. (imH)[trans-RuCl4(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.

Keywords: ruthenium, dimethylsulfoxide, anticancer, antimetastatic, inorganic medicinal chemistry

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Article Details

VOLUME: 4
ISSUE: 15
Year: 2004
Page: [1525 - 1535]
Pages: 11
DOI: 10.2174/1568026043387421
Price: $58

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