Platinum anticancer drugs

A genetic profile on the basis of SNPs would be more than useful for Chemotherapy-Induced Peripheral Neurotoxicity (CIPN) risk stratification, prior to start treatment. CIPN is a potentially severe and long-lasting side effect of commonly employed anticancer drugs platinum compounds, taxanes, proteasome inhibitors, vinca alkaloids, and epothilones they are used every day to treat... 

Many complexes and coordination compounds exist as isomers, compounds that contain the same numbers of the same atoms but in different arrangements. For example, the ions shown in (13a) and (13b) differ only in the positions of the Cl ligands, but they are distinct species, because they have different physical and chemical properties. Isomerism is of more than academic interest for example, anticancer drugs based on complexes of platinum are active only if they are the correct isomer. The complex needs to have a particular shape to interact with DNA molecules. 

X 16.101 cis-Platin is an anticancer drug with a structure jQ that can be viewed on the Web site, (a) What is the formula and systematic name for the compound cis-jf Platin (b) Draw any isomers that are possible for this compound. Label any isomers that are optically active, (c) What is the coordination geometry of the platinum atom ... 

Hambley and co-workers have reported the synthesis, DNA cross-linking, and in vitro anticancer properties of a platinum(II) complex that was designed to bind the macromolecule in an interstrand rather than intrastrand manner,162 the latter being the dominant mode of DNA-binding by platinum anticancer drugs such as cisplatin. The complex [PtCl2(hpip)] ((46) ... 

There are numerous platinum(IV) complexes with nitrogen donors, most of which have been prepared as potential anticancer drugs or in the study of the reactions of such drugs. These compounds are described below in Section 6.5.6.5. 

Dhar, S. Lippard, S. J. Current Status and Mechanism of Action of Platinum-Based Anticancer Drugs. In Bioinorg. Med. Chem. 79-95 (Wiley-VCH Verlag) (2011). 

Wu, B., Davey, G. E., Nazarov, A. A., Dyson, P. J. Davey, C. A. Specific DNA Structural Attributes Modulate Platinum Anticancer Drug Site Selection and Cross-Link Generation. Nucleic Acids Res. 39, 8200-8212 (2011). 

Feazell, R.P. et al. (2007) Soluble single-walled carbon nanotubes as longboat delivery systems for platinum(IV) anticancer drug design. Journal of the American Chemical Society, 129 (27), 8438-8439. 

Rosenberg, B. Platinum Complexes for the Treatment of Cancer. Why the Search goes on. In Cisplatin Chemistry and Biochemistry of a Leading Anticancer Drug Lippert, B., Ed. Wiley-VCH New York, 1999 pp 3-30. 

CONTROLLING PLATINUM, RUTHENIUM, AND OSMIUM REACTIVITY FOR ANTICANCER DRUG DESIGN... 

In our group, a major part of our research is devoted to the design of new anticancer drugs. Our recent efforts towards the discovery of new platinum-, ruthenium- and osmium-based anticancer agents provide the topic for this account and a section is devoted to each metal. We focus on recent results from our lab in the context of other developments and related research in this field (hence our coverage of the field is focused on these areas and is not comprehensive). 

Fig. 1. Molecular structures of (a) some platinum(II)-based anticancer drugs currently used in the clinic (b) satraplatin, a platinum(IV) prodrug currently in clinical trials.

Pt(TV) Prodrugs. Platinum(IV) complexes have been widely studied as potential prodrugs that avoid the limitations of the cisplatin class of anticancer drugs. Indeed, the Pt(IV) compound satraplatin [Pt(cha)Cl2(OAc)2(NH3)] (cha, cyclohexylamine) is currently in clinical trials for treatment of hormone-refractory prostate cancer (Fig. 1) (22). Satraplatin is the first orally bioavailable platinum derivative under active clinical investigation and is particularly attractive because of the convenience of administration, milder toxicity profile, and lack of cross-resistance with cisplatin. These results are promising and support the idea that platinum(IV) complexes offer the opportunity to overcome some of the problems associated with cisplatin and its analogs. 

Recent reviews in the field of platinum anticancer drugs focus on platinum-nucleobase chemistry [7], biological processing of platinum-modified DNA [8], trans-platinum anticancer drugs [5], cisplatin and derived anticancer drugs [4,9], proteins and cisplatin [10], trans-diam-mineplatinum(II) and nucleic acids [11], and catalytic activity and DNA [12], just to mention a few. The aim of this review is to explore the chemistry in the interaction of various platinum compounds with nucleic... 

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