Antimetabolite agents

Antimetabolites. AntimetaboHtes, which represent one of the earliest groups of anticancer agents, are Hsted ia Table 1. Stmctures are showa... 

Anticancer antimetabolites Antimetabolic agents An-tineoplastic antimetabolites... 

Some newly introduced pyrimidine analogs (e.g., azacitidine and decitabine) differ in their mechanism of action to such a degree from the other antimetabolites that they are subgrouped under the heading DNA de- or hypomethylating agents (see below). 

Antimetabolites interfere with normal metabolic pathways. They can be grouped into folate antagonists and analogues of purine or pyrimidine bases. Their action is limited to the S-phase of the cell cycle and therefore they target a smaller fraction of cells as compared with alkylating agents. 

Cancer, Molecular Mechanism of Therapy Antineoplastic Agents Alkylating Agents Antimetabolites... 

One commonly used agent is the antimetabolite 5-fluorouracil (5-FU), which is frequently used as an adjuvant therapy in conjunction with surgical excision in the treatment of solid tumors. p53 can directly trigger apoptosis in cells exposed to 5-FU in vitro [1]. In addition, there is a substantial amount of clinical... 

In vivo azathioprine is rapidly converted into its active metabolite 6-mercaptopurine by the enzyme thiopurine methyltransferase (TPMT). The active agent inhibits IMPDH function. Furthermore, it also acts as antimetabolite of the RNA and DNA synthesis particularly in T-lymphocytes leading to cell death. Due to genetic polymorphism of TPMT, therapy may fail, thus it is currently discussed whether individual patients should be monitored before the use of azathioprine. 

The answer is b. (Hardmanr p 1241.) Busulfan is an alkylating agent that, in contrast to other alkylators, is an alkylsulfonate. Thioguanine is a purine antimetabolite. Bleomycin is classified as a chemotherapeutic... 

Anticancer drugs act on cells in active proliferation and may interfere with a specific phase of the cell cycle or act independently from it. Some of these drugs are naturally occurring compounds, identified in plants or microorganisms, some are synthetic chemicals. Among the major classes of chemotherapeutics include antimetabolites, alkylating agents, inhibitors of the... 

Methotrexate is an antimetabolite chemotherapeutic agent, which may also be used for severe resistant psoriasis. The dose is usually administered orally once a week. Haematological and biochemical parameters are monitored throughout treatment. 

Ciclosporin, a calcineurin inhibitor, is a potent immunosuppressant useful in the prevention of rejection in organ transplants and grafting procedures. Ciclosporin is markedly nephrotoxic. Vincristine is a vinca alkaloid cytotoxic agent fluorouracil and methotrexate are both antimetabolite cytotoxic agents and bleomycin is a cytotoxic antibiotic. 

The fact that many agents which interrupt the synthesis of pyrimidine nucleotides from orotic acid in animals can also inhibit the growth of experimental neoplasms suggests a search for additional antimetabolites whose locus of action is in this metabolic sequence. Two in vitro biological screening systems were developed for this purpose [202—207]. From a study of systems with oxidative energy sources, 5-bromo-[208—209] (Villa), 5-chloro-[210] (Vlllb) and 5-diazo-orotic acid [211] (IX) were found to inhibit the conversion of orotic acid to the uridine nucleotides by 40—100 per cent [202]. 

The pyrimidine 5-fluorouracil (64) is used extensively in the clinic as an antimetabolite antitumor agent. As a consequence of poor absorption by the oral route, the drug is usually administered by the intravenous route. A rather simple latent ated derivative, tegafur (66), has overcome this limitation by providing good oral absorption. Reaction of 5-fluorouracil with trimethylsilyl chloride in the presence of base gives the disilylated derivative (65). Reaction of this with dihydrofuran (obtained by dehydro-... 

Drags used to treat cancer are subdivided into six groups antimetabolites, alkylating agents, antibiotics, drags isolated from plants, hormones, and a group of substances not included in the classifications listed above, which are examined in another section. 

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