Ruthenium Antitumor Agents

Cisplatin, carboplatin, and other platinum analogues were the first coordination compounds to show anticancer properties. Not surprisingly, that serendipitous discovery inspired a search for other such compounds. The palladium analogues of cisplatin had no such parallel properties, but some titanium and molybdenum asymmetrically substituted acetylacetonato complexes did. Ruthenium complexes were the next such breakthrough. First the cis-tetraamminedichlororuthenium(III) chloride and fac-triamminetrichlororuthenium(III) showed excellent anticancer 

Three ruthenium anticancer compounds a) imidazolium trans-tetrachlorobis(imidazole) ruthenate(III), Him trans-[RuCl4(im)2] (6) indazolium trans-tetrachlorobis(indazole) ruthenate(III), Hind trans-[RuCl4(ind)2]  

Coordination compounds have a wide variety of applications. Complexes of monodentate ligands are used in qualitative analysis, identification of copper(II) and iron(II), dyes [Prussian (TurnbuU s) blue], the cyanotype printing process, the separation of gold and silver from their ores, the purification of nickel, and as fixers in black-and-white photography. 

Synthetic detergents are composed of a surfactant and a builder. The latter is often a chelating agent such as the tripolyphosphate ion. It sequesters hard-water cations, rendering them incapable of interfering with the surfactant. Phosphates, however, are nutrients and have been implicated as a major cause of advanced eutrophication. A variety of phosphate replacements have been considered including 

Almost 40 years ago, cisplatin, a square planar coordination compound of platinum(II), was found to be an effective antitumor agent. It forms complexes with some of the nitrogen bases of DNA, producing mutations during the replication of cancer cells. Second-generation square-planar platinum(II) complexes such as carboplatin and oxaliplatin that have less severe side effects are now available. Octahedral platinum(IV) complexes such as satraplatin as well as triplatin, a tri-nuclear platinum(II) complex, are in various stages of development. A new class of ruthenium(III) anticancer complexes hold promise of targeting additional cancer types with fewer side effects. 

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Both Ru(II) and Ru(III) complexes are known to bind DNA preferentially at N7 of G but also to A and C bases (182, 183). Although most ruthenium antitumor agents have two reactive coordination sites, GG intrastrand cross-links on DNA do not appear to form readily. The only example appears to be the adduct of 27 with GpG, which has been structurally characterized by NMR spectroscopy (184). In this complex, the two N7-coordinated guanines adopt a head-to-head conformation and the two bases are strongly destacked. 

Transition-metal based compounds constitute a discrete class of chemotherapeutics, widely used in medicine as antitumor agents.56 Several ruthenium complexes enable the body to catalyze oxidation and reduction reactions, depending on the physiological environment, and have attracted much interest as alternative antitumor drugs in the treatment of cancer cells resistant to cisplatin in cancer... 

Ruthenium Antitumor and Nitrogen Oxide Scavenging Agents... 

Recently Clarke et al. have advanced the proposal that antitumor RudDammine complexes may excert their action by redox cycling in the presence of oxygen and a reducing agent with formation of active oxygen species which cleave DNA. The most prominent member of the metal group is cis-DDP. Evidence for electron transfer is provided by electrochemical behavior , radiosensitization" and nephrotoxicity s 2-74, Anticancer activity is displayed by a number of other metals and metalloids in compound form s -- . The possibility exists that the ultimate active forms of the various metals may be the DNA complexes, for example, with copper s and ruthenium . ET and oxy radical formation are known to occur with enzymes that contain copper s . 

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