Cancer cell-targeted suicide

The answer is c. (Murray, pp 48-73. Scriver, pp 4571-4636. Sack, pp 3-17. Wilson, pp 287-317.) Since rapidly multiplying cancer cells are dependent upon the synthesis of deoxythymidilate (dTMP) from deoxy-uridylate (dUMP), a prime target in cancer therapy has been inhibition of dTMP synthesis. The anticancer drug fluorouracil is converted in vivo to fluorodeoxyuridylate (FdUMP), which is an analogue of dlJMP FdUMP irreversibly forms a covalent complex with the enzyme thymidylate synthase and its substrate N5,N10-methylene-tetrahydrofolate. This is a case of suicide inhibition, where an enzyme actually participates in the change of a substrate into a covalently linked inhibitor that irreversibly inhibits its catalytic activity. 

The ability of quinazoline to enter the xanthine oxidase active site, and the presence of an active site nucleophile near the alkylating center, very likely accounts for enzyme inactivation by these hydroquinones. The quinone (696) acts as an oxidizing suicide substrate. It is able to enter the xanthine oxidase active-site, and by the enzyme reductive action and HCl elimination it becomes a reductive alkylating agent (698) targeted towards cellular structures important to the cancer cell <88JOC6099>. 

A controversial family of drugs at present, the selective serotonin reuptake inhibitors (SSRI, implicated in childhood suicide) have been followed using MRI to study choline metabolic rates . A common characteristic consistently revealed by MRS studies in cancer cells and solid tumours is the elevation of phosphatidyl choline and total choline-containing compounds - a possible target for early detection and therapy ... 

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