Platinum drug cisplatin

Evolution of the first generation platinum drug cisplatin into later generation drugs. 

Although the second generation of platinum drugs is less toxic than cisplatin, many appear to be cross-resistant with cisplatin. Requirements which are influencing the search for new generations of active complexes include (1) lower toxicity to normal cells than cisplatin, (2) activity against tumors with acquired cisplatin resistance, (3) activity against a wider spectrum of types of cancer, and (4) oral activity. 

Pinto AL, Lippard SJ. Binding of the antitumor drug cis-diamminedichloro-platinum(II) (cisplatin) to DNA. Biochem Biophys Acta 1985 780 167-180. 

Antitumor drugs cisplatin as, history, 37 175-179 platinum compounds future studies, 37 206-208 resistance to, 37 192-193 second-generation, 37 178 Antiviral agents, 36 37-38 AOR, see Aldehyde oxidoreductase Aphanothece sacrum, ferredoxins, amino acid sequence, 38 225-227 Apo-calcylin, 46 455 Apo-caldodulin, 46 449-450 Apoenzyme, 22 424 Apoferritin biosynthesis, 36 457 cystalline iron core, 36 423 Fe(III)distribution, 36 458-459 Fe(II) sequestration, 36 463-464 ferroxidase centers, 36 457-458 iron core reconstruction in shell, 36 457 mineralization, 36 25 Mdssbauer spectra, 36 459-460 optical absorbance spectra, 36 418-419 subunit conformation and quaternary structure, 36 470-471... 

There have been numerous studies of the interaction of the highly effective anticancer drug cisplatin, c/5-[Pt(NH3)2Cl2], with DNA. The majority of these studies have concentrated on the adduct formed between the platinum(II) ion and two adjacent guanine bases (G) on one strand of DNA this is the adduct most frequently... 

Of the platinum-based drugs, cisplatin or cf -diarnmincdichloroplatinum (II) has been the most studied in treatments of cancerous tumours. Quantities of the drug administered in treatments must be carefully controlled because of appearances of side effects, primarily nephrotoxicity and nausea in patients. In some studies, ultrafilterable cisplatin, or free platinum in blood serum or plasma has been differentiated from platinum bound to proteins (Goel et al., 1990). HPLC has been used extensively in separations of intact cisplatin from other species. An anion-exchange column was connected to a post-column reactor and a UV-spectrophotometer for measurements of cisplatin concentrations in plasma and urine (Kizu et al., 1995). The detection limit was 20 nmol dm-3. Modes of action... 

T) Do direct chemical interactions occur between rescue agents and platinum compounds (such as the drugs cisplatin and carboplatin transpla-tin), and between the relevant model compounds (such as Ptn(dien), or perhaps the kinetically faster reacting Pd11 compounds) Which interaction products are formed in vivo (structure, kinetics) This topic has been largely neglected in the literature. 

Neurotoxicity has been observed both preclinically and clinically with some platinum drugs including cisplatin and tetraplatin (Ormaplatin ). For example, in rats after 6 weeks of treatment with cisplatin twice weekly at 2 mg/kg, a significant decrease (17%) in sensory nerve conduction velocity was observed while the motor nerve conduction velocity was unaffected. Tetraplatin at 1 mg/kg twice weekly caused a 14% decrease in sensory nerve conduction velocity. In parallel experiments in the rat, twice weekly treatment with JM216 at 25 mg/kg did not affect the sensory nerve conduction velocity [24],... 

The success of cisplatin and carboplatin in treating cancer, combined with the intrinsic and acquired resistance of many tumors to traditional platinum chemotherapy, has generated considerable interest in developing next-generation platinum drugs. Since the discovery of the antitumor activity of cisplatin, researchers have reported the synthesis, characterization, and antitumor activity of thousands of platinum compounds [1] [2]. The previous two chapters in this section describe the promising activity of novel multi-nuclear Ptn and orally active PtIV complexes [3] [4],... 

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