Antitumor agent, cisplatin

Bone. Although bone is a relatively inert tissue, it can accumulate such substances as tetracyclines, lead, strontium, and the antitumor agent cisplatin. These substances may accumulate in bone by absorption onto the bone crystal surface and eventually be incorporated into the crystal lattice. Tetracycline deposition during odontogenesis may lead to a permanent yellow-brown discoloration of teeth, dysplasia, and poor bone development. Lead can substitute for calcium in the bone crystal lattice, resulting in bone brittleness. Bone may become a reservoir for the slow release of toxic substances, such as lead and cisplatin. 

Cis and trans isomers of square-planar complexes are common many platmum(ll) examples are known. The isomers of [Pt(NH3)2012] are shown in Figure 9.5. The cis isomer is used in medicine as the antitumor agent cisplatin. Chelate rings can enforce a cis structure if the chelating ligand is too small to span the trans positions. The distance across the two... 

Chatteijee et al., 1984 Sens et al., 1988), and cyclosporine (TrifiUis et al., 1984). Studies reported by Tay et al. (1988) in rabbit proximal tubule cultures with cisplatin revealed biochemical effects upon DNA synthetic activty that correlated with in vivo histochemical effects of this antitumor agent in animals. With respect to studies involving mercuric chloride and aminoglycoside antibiotics in primary renal cultures, light and electron microscopy revealed similar patterns of cellular pathology in vitro as compared to in vivo exposure in animals (Chatteijee et al., 1984 Aleo et al., 1987). 

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... 

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... 

The Ru(III) complexes (imH2)2[Ru(imH)Cl5] and mms-(imH2) [Ru(L)2Cl4] (L = imidazole, 1-methylimidazole, 2-methylimidazole, 4-methylimidazole) have been shown to be promising antitumor agents of comparable activity to cisplatin. The mode of action of these complexes is unknown (87IC844, 87IC4366). 

Editor s comment This article is taken in large part from a review article published more than twenty years ago in Interdisciplinary Science Reviews, Vol. 3, No. 2, pp 134-147 (1978). It tells the story of the discovery of cisplatin and reflects on its possible mode of action as an antitumor agent. While some of the ideas may have been revised or discarded today, the article represents a unique personal account of the discovery and at the same time is a beautiful example of science history. The chapter on the clinical results has been deleted, since the present status is covered in an up-to-date manner in this book s contribution by O Dwyer and co-workers. The editor wishes to thank John Wiley Sons Limited for permission to reproduce this work. 

The book contains 22 chapters and is divided into six Parts. The first chapter is by Rosenberg who, in a very personal manner, describes the time from the discovery of cisplatin to its acceptance as an established anticancer drug in the late seventies. The chapter in Part 2, written by O Dwyer and colleagues, gives a topical account of the present clinical status of Pt antitumor agents. 

Morinaga (6) observed that the stilbene derivative (Z)-l-(3-(2-amino-3-hydroxypropamidc)-4-mcthoxyphcnyl)-2-(3,4,5-trimethoxyphenyl)cthanc, (VI), in conjunction with the neoplasm inhibitor Cisplatin , (NH3)2Cl2Pt(II), strongly inhibited mitosis without patient weight loss associated with other antitumor agents such as Vindesine . 

Figure 11 Clinically used platinimi antitumor agents (a) cisplatin (b) carboplatin (c) nedaplatin (d) oxahplatin (e) lobaplatin...

Sun, J., Blaskovich, MA., Knowles, D., Qian, Y., Qhkanda, J., Bailey, R.D., Hamilton, A.D., and Sebti, S.M (1999). Antitumor efficacy of a novel class of non-thiol-containing peptidomimetic inhibitors of farnesyltransferase and geranylgeranyltransferase 1 combination therapy with the cytotoxic agents cisplatin, Taxol, and gemcitabine. Cancer Res 59 4919-4926. 

---