Pyrimidine antagonists

The answer is a. (Hardman, pp 1247-1251.) 5-Huorouracil is a pyrimidine antagonist that has a low neurotoxicity when compared with other fluorinatecl derivatives however, its major toxicities are myelosup-pression and oral or gastrointestinal ulceration. Leukopenia is the most frequent clinical manifestation of the myelosuppression... 

Antimetabolites are subdivided into three groups folic acid antagonists (methotrexate), purine antagonists (mercaptopurine, thioguanidine), and pyrimidine antagonists (fluo-rouracil, floxuridine, cytarabine). 

The pyrimidine antagonists inhibit the biosynthesis of pyrimidine nucleotides or interfere with vital cellular functions, such as the synthesis or function of nucleic acids. The analogues of deoxycytidine and thymidine that are used are inhibitors of DNA synthesis while 5-fluorouracil (5-FU) an analogue of uracil, is an inhibitor of both RNA function and of the synthesis of thymidylate (see Fig. 2). PALA (N-phosphonoacetyl-L-aspartate), an inhibitor of as-... 

Maring JG DPD phenotyping in human volunteers and a DPD-deficient patient by assessing uracil pharmacokinetics after an oral oral uracil test dose a preliminary report. In New Insight of Pyrimidine Antagonists Chemotherapy, Chapter 5, pp. 102-111, Thesis, University of Gronigen, NL, 2005. 

Site of action Like the other purine and pyrimidine antagonists, ara-C must be sequentially phosphorylated to the corresponding nucleotide, cytosine arabinoside triphosphate (ara-CTP), in order to be cytotoxic. It is S-phase (hence cell-cycle) specific. Ara-C is also incorporated into DNA and can terminate chain elongation. It can also inhibit the reduction of CDP to dCDP. 

Purine antagonists (azathioprine, mercaptopurine, tioguanine) and pyrimidine antagonists (cytarabine, fludarabine, 5-fluorouracil) similarly deprive cells of essential metabolites. 

The anabolites of purine and pyrimidine antagonists may be incorporated into nucleic acids. In this event, port of their antitumor effect might result from malfunction of further macromolecular. synthesis because of the abnormal nucleic aeids. ... 

Antimetabolites compete with normal endogenous substrates and cause inhibition of the processes that require those substrates. Examples include purine and pyrimidine antagonists, which prevent nucleic acid replication and cellular division in cancer chemotherapy. Another example is methotrexate, which can inhibit folic acid metabolism. 

What pyrimidine antagonist can work like a central line of 5-FU ... 

Antimetabolites (SEDA-29, 551) Purine antagonists, pyrimidine antagonists, antifolate drugs, phosphatidylcholine antagonists, adenosine deaminase inhibitors... 

C8H11N3O6 245.191 Pyrimidine antagonist and bacteriostat. Antiviral agent active against human smallpox and viral eye infections. Antineoplastic. Needles (Et0H/Et20). 

Many potent pyrimidine antagonists have also been obtained by isosteric replacement in the heterocyclic ring. Oxonic acid (Fig. 12) an analogue of orotic acid, prevents the conversion of the latter to orotidylic acid (Fig. 2). A later stage of pyrimidine biosynthesis, the decarboxylation of orotidylic acid to form uridylic acid (Fig. 2) is strongly inhibited by 6-azauracil (Fig. 12 this chemical should be correctly termed 4-azauracil). The riboside of 6-azainacil acts on the same pathways as the base, but its inhibition of the orotidylate carboxylase enzyme is some 20 times more potent... 

In a later, more comprehensive study, the effect of the purine and pyrimidine antagonist, 6-thioguanine (6-TG), was examined in detail [134]. The dose-dependent effect of 6-TG on the heat flow rate of T-lymphoma CCRF-CEM cells was examined and the results are depicted in Figure 41. The transient spike at the time of introducing the drug represents the heat of dilution of the drug and, more particularly, of the vehicle to dissolve the 6-TG, that is dlmethylsulphoxide (DMSO). 

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