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Antifolate: Wikis


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Antifolates are drugs which impair the function of folic acids.[1] Many are used in cancer chemotherapy, some are used as antibiotics or antiprotozoal agents.

A well known example is Methotrexate. This is a folic acid analogue, and owing to structural similarity with it binds and inhibits the enzyme dihydrofolate reductase (DHFR), and thus prevents the formation of tetrahydrofolate. Tetrahydrofolate is essential for purine and pyrimidine synthesis, and this leads to inhibited production of DNA, RNA and proteins (as tetrahydrofolate is also involved in the synthesis of amino acids serine and methionine).

Since, antifolates interfere with metabolism (of nucleotides), they are categorized as antimetabolites.

Other antifolates include trimethoprim, pyrimethamine and pemetrexed.

Many are primarily DHFR inhibitors but raltitrexed is an inhibitor of thymidylate synthase, and pemetrexed inhibits both and a third enzyme.



Antifolates act specifically during DNA and RNA synthesis, and thus are cytotoxic during the S-phase of the cell cycle. Thus they have a greater toxic effect on rapidly dividing cells (such as malignant and myeloid cells, and GI & oral mucosa), which replicate their DNA more frequently, and thus inhibits the growth and proliferation of these non-cancerous cells as well as causing the side effects listed.



Side effects

The antifolate action specifically targets the fast-dividing cells, and tend to have adverse effects on the bone marrow, skin and hair.


Many new drugs are under development to reduce antifolate drug resistance.[2][3]



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