Biochemical Modulation of 5-Fluorouracil with Pyrimidines, Purines and their Nucleosides

  • Giovanni Santelli
Part of the Developments in Oncology book series (DION, volume 47)


Attempts at improving the selectivity of FUra by biochemical modulation with purine and pyrimidines were carried out soon after the synthesis and early clinical trials of FUra (1). The coupling of an antimetabolite with physiological metabolites received much attention in those years after the successful use of the pair methotrexate-folinic acid (2, 3). The hope was to discover a similar combination containing FUra that would allow its administration beyond the maximal tolerated dose and possibly achieve a better selectivity for tumor cells. After it became clear that the metabolic pathways involved in the activation of FUra to cytotoxic nucleotides were complex, and regulated by enzymes in the presence of feed-back mechanisms, a whole new area was opened to investigation. After the initial disappointing results, this approach was almost abandoned, however, recently some important new data concerning the mechanism of action of FUra have revitalized the field. I will outline in this review the most important contributions to this area, focusing on the use of pyrimidines, purines and their nucleosides, as well as the need for future studies.


LoVo Cell Purine Nucleoside Orotic Acid Purine Nucleoside Phosphorylase Ehrlich Ascites Tumor Cell 
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© Martinus Nijhoff Publishing, Boston 1986

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  • Giovanni Santelli

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