Platinum Cisplatin

Os-platinum (cisplatin) binds to intracellular DNA, causing both interstrand and intrastrand cross-linking. It is a cell-cycle phase nonspecific agent. Os-platinum, which is ineffective orally, is used for testicular, bladder, and head and neck cancers. It precipitates nephrotoxicity, ototoxicity, and gastrointestinal injury. 

Representative Chemicals c/s-Dichlorodiammine platinum (cisplatin) c/s-Platinum chloride Potassium chloropaletinite... 

The determination of Au and Au isotopes in fallout samples produced in the Au(n, 2n) Au and Au(n, y) Au neutron activation reactions has been described . Fallout samples containing neutron activated nuclides and actinides have been collected with polyperchloroethylene filters. Counting procedures showed the concentrations of Au to be 0.24-0.42 ngg in tumour-type tissues . 1,2-Diarylethylenediamine Pt complexes have been examined by determining via NAA the content of platinum in tumour tissue and in the different organs of mice. The measurements of the induced radioactivity of Au served as indications of the Pt concentration . The contribution of this type of radiation is given. Irradiated platinum has been purified from Au by extraction from acidic solutions with ethyl acetate . The distribution of cis-dichlorodiamine platinum ( cisplatin ) in various organs of mice has been determined . 

Cis-diamminedichloride platinum, cisplatin, shows a square-planar configuration with a central Pt atom surrounded by Cl atoms and NH3 in the cis position in the horizontal plane. There is evidence that the complex becomes aquated intracellularly to form positively charged Pt species that are likely to interact with nucleophilic sites. The purine and pyrimidine bases of DNA possess such receptor sites and thus provide the locus for effective intracellular binding. The biologically important lesions are most likely to be interstrand and/or intrastrand cross-links (Zwelling and Kohn 1979). 

Carboplatin (96) is significantly less toxic in the clinic than cisplatin. Most particularly, it is much less nephrotoxic. Use of a bidentate ligand also ensures formation of a ds complex. Its synthesis begins with cis-diammine platinum diiodide (94) which is reacted with silver sulfate to give cis-diaquodiam mine platinum sulfate (95). This is reacted with the barium salt of 1,1-cyclo-butanedicarboxylic acid to yield carboplatin [23],... 

The only prominent antitumor tetravalent platinum complex so far is iproplatin (102). In vitro it has been shown to cause interstrand DNA-breaking and cross linking. Free radical scavengers inhibit these effects. The complex is less neurotoxic and less nephrotoxic than cisplatin. Its synthesis begins with hydrogen peroxide oxidation of cis-dichlorobis(isopropvlamine) platinum (100) to the dimethylacetamide complex 101. The latter is heated in vacuum to liberate iproplatin [25]. 

Cisplatin, Pt (NH3)2Cl2, is a chemotherapeutic agent that disrupts die growth of DNA. If die current cost of Pt is 1118.0/troy ounce (1 troy oz = 31.10 g), how many grams of cisplatin can you make with three thousand dollars worth of platinum How many pounds ... 

Figure 3.116 Platinum compounds studied for possible anti-tumour activity. I, ris-Dichlorodi-ammineplatinum(II) cisplatin, platinol NSC 119875 neoplatin platinex. II, a.s-Diammine(l,l-cyclobutanedicarboxylato)platinum(II) JM-8 paraplatin NSC 241240. Ill, Oxiplatin. IV, Tetraplatin. V, Amminediacetatodichloro(cyclohexylamine)platinum(IV). VI, cis-Dich oro-trans-dihydroxy-cis-bis(isopropylamine)platinum(IV) iproplatin JM-19 CHIP NSC 256927.

Cisplatin was discovered fortuitously by observing that bacteria present in electrolysis solutions could not divide. It is hypothesized that in the intracellular environment, a chloride is lost and replaced by a water molecule. The resulting species is an efficient bifunctional interactor with DNA, forming platinum-based cross-links similar to that formed by alkylating agents. 

Other subgroups of alkylating agents are the nitrosoureas (examples carmustine, BCNU lomustine, CCNXJ) and the triazenes (example dacarbazine, DTIC). Platinum derivatives (cisplatin, carboplatin, oxaliplatin) have an action that is analogous to that of alkylating agents (formation of crosslinks) and therefore are appended to this class, as well. 

Cisplatin — see Platinum, cw-dichlorodiammine-Cis-transisomerization, 1, 467 Citrate lyase activation... 

Ali, B.H. AI Moundhri, M.S. (2006). Agents ameliorating or augmenting the nephrotoxicity of cisplatin and other platinum compoimds a review of some recent research. Food and Chemical Toxicology, Vol. 44, No.8, (August 2006), pp. 1173-1183, ISSN 0278-6915. 

Platinum regimens are also the treatment of choice in extensive disease, and many studies have failed to show superiority to the EP regimen as first-line treatment. A combination of irinotecan and cisplatin in one Japanese study demonstrated an increased median survival time by approximately 3 months... 

Oxaliplatin (Eloxatin ) is similar to other platinum analogs (e.g., cisplatin) in that it binds to the N-7 position of guanine, which results in cross-linking of DNA and double-stranded DNA breaks.26,40 Oxaliplatin differs from cisplatin in that the DNA damage induced by oxaliplatin may not be as easily recognized by DNA repair genes often seen in colorectal cancer. Oxaliplatin, in combination with 5-FU-based regimens, is indicated for the first- and second-line treatment of metastatic colon cancer, as well as the adjuvant treatment of colon cancer. 

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) ... 

Stein and co-workers have reported the structure of an unusual tetranuclear platinum(II) complex possessing both ammine and carbonato ligands.325 During a study of the reaction of cisplatin with Ag+, followed by the addition of 2 -deoxyuridine to afford platinum blue -like products from aqueous solution (pH < 2), a colorless minor product was isolated from the reaction mixture. X-ray crystallography confirmed that the product was a cyclo tetra-cation... 

Cisplatin is a platinum complex (platinum dichloride and two ammonia molecules) used as a cytostatic agent against cancer. The molecule cross-links DNA strands, thus leading to cell death. 

The main uses for platinum are as a catalyst in the catalytic converter and in fuel cells. And of course platinum, a very expensive metal, is used in jewellery. However, certain platinum-containing compounds are chemotherapeutic agents, examples being cisplatin, carboplatin and oxaliplatin. This explains the synthetic interest in platinum compounds. 

Cisplatin, (ds-[PtCl2(NH3)2], also known as cis-DDP) ((1), Figure 2) is perhaps the best known example of a small molecule metal-containing drug. The clinically used platinum complexes are shown in Figure 2. The history of the discovery and development of cisplatin remains a remarkable scientific story.33 Its use and effectiveness in cancer chemotherapy since the entry into the clinic in the late 1970s has been thoroughly documented.34-36 Cisplatin is cited for treatment of... 

Resistance to cisplatin is multifactorial and has been shown to be due to a combination of decreased cellular accumulation of cisplatin, increased efflux of platinum from the cell,... 

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