Anticancer compounds cisplatin properties

As mentioned in the introduction, metallocene-type complexes based on the early transition metals were evaluated as anticancer compounds shortly after the discovery of cisplatin. While the biological activity of each of the metallocene dihalides is unique, titanocene dichloride 7 has been the subject of a number of studies and even entered clinical evaluation, although evaluation was discontinued (not due to its anti-proliferative properties), principally due to formulation problems, despite showing superior activity to certain cancers than other established drugs. This class of compound continues to be modified and studied for anticancer activity, for example, the titanocene-type derivative of tamoxifen 1, described above, and other developments described below. 

The first report on the anticancer properties of ruthenium was published in 1976 when the Ru(III) compound /ac-[RuC13(NH3)3] (Fig. 11) was found to induce filamentous growth of Escherichia coli at concentrations comparable to those at which cisplatin generates similar effects (49). This Ru(III) complex and related compounds such as cis-[RuCl2(NH3)4]Cl illustrated the potential anticancer activity of ruthenium complexes, but insolubility prevented further pharmacological use. Since these initial studies, other Ru(III) complexes have been studied for potential anticancer activity, and two compounds, NAMI-A (50) and KP1019 (51), are currently undergoing clinical trials. Remarkably,... 

Fig. 13.1 Cisplatin and some second generation compounds with anticancer properties...

The square-planar geometry (see Figs. 8.18b,c) is common for four-coordinate complexes of Au, Ir, Rh", and especially common for ions with the valence electron configurations Ni ", Pd ", and for example. The Ni " ion forms a few tetrahedral complexes, but four-coordinate Pd " and Pp" are nearly always square planar. Square-planar complexes of the type MA2B2 can have isomers, as illustrated in Figures 8.18b and c for cis- and trd ws-[Pt(NH3)2Cl2]. The cis form of this compound is a potent and widely used anticancer drug called cisplatin, but the trans form has no therapeutic properties. 

Due to the anticancer activity of some amine-coordinated Pt compounds, there has been extensive interest in the complexes of Pt with oligonucleotides and nucleotides. These Pt complexes normally have square planar geometry and, in the case of bases and dinucleotides, can template more extensive supramolecular structures. Certain cw-Pt complexes are highly effective anticancer agents, the most famous being cisplatin or d5-diamminedichloroplatinum(II) and a related compound, carboplatin, cM-diammine(cyclobutane-l,l-dicarboxylato)platinum(II). There have been extensive studies of the coordination properties of Pt compounds with nucleic acid bases to further understand the effect of these drugs on DNA structure and function. ... 

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... 

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