Produce Anti-Tumour Agents

Platinum coordination complexes have been investigated as potential anticancer agents since 1972. The most successful of these is the cis dichlor-diammine platinum(II) complex which is particularly effective for the treatment of ovarian and testicular carcinomas. However, effective therapy requires high doses, typically 4.0/umol (825/ig)kg-1 given intravenously, which produce unpleasant and toxic reactions. Pharmaco-kinetic studies of the various Pt species in plasma indicate that the active species is of low molecular weight and the protein bound Pt species is apparently inactive [106]. Further work is needed to identify the active species and to develop therapeutic procedures that produce maximum anti-tumour activity with minimum toxicity. 

The high anti-tumour selectivity of the triazenes and their broad spectrum of action requires further investigation since it may eventually enable the design of agents for clinical use which maintain their anti-tumour specificity but do not break down into products which are toxic but not tumour inhibitory. The role of formaldehyde produced by the active dimethyl derivatives but not by the inactive diethyl analogues, may be important. It has also recently been proposed that toxic products formed by triazenes may be neutralised by factors in the cytoplasm of normal tissues but not in sensitive tumour cells77. ... 

Mitomycin C, an antibiotic produced by fermentation of streptomyces, has been used extensively in Japan for the treatment of stomach cancer which is prevalent in that country. It probably acts after conversion into an alkylating agent in vivo, and it also contains quinone and urethane moieties which may contribute to its anti-tumour effect. A related series of compounds, the pyrol-lizidine alkaloids, occur in a variety of plants and are known to cause acute liver cytotoxicity when accidentally ingested93). Like mitomycin C, these agents are almost certainly metabolised in vivo by liver microsomes to alkylating agents which cause the liver toxicity. Some of these alkaloids have antitumour properties, presumably because the active metabolite formed in the liver is stable enough to reach the tumour. 

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