Antimetabolites in Chemotherapy

Antimetabolites are compounds with a structure similar to other molecules that the cells in your body use as part of their metabolism. When cells mistake the antimetabolite for the compound they would ordinarily use, they are unable to process it properly and vital processes in the cell grind to a halt, typically resulting in the death of the cell. There are three different classes of antimetabolite drugs often used to treat cancer.

Purine Antagonist

• Purines are organic compounds that consist of two fused rings. Adenine and guanine, two of the bases that make up the genetic code in DNA, are both purines. Purine antagonists are drugs that inhibit purine nucleotide synthesis, preventing the cell from efficiently replicating its DNA, or are incorporated into DNA in the place of a purine base. Since cancer cells are dividing rapidly, they must replicate their DNA frequently, and drugs that inhibit DNA synthesis and replication can cause the death of the cancer cells. 6-mercaptopurine, dacarbazine and fludarabine are all drugs in this category.

Pyrimidine Antagonist

• Thymine, cytosine and uracil are DNA or RNA bases that are categorized as pyrimidines, members of a class of organic compounds consisting of a single nitrogen-containing ring. Pyrimidine antagonists are similar to purine antagonists except that they target synthesis of pyrimidine nucleotides or are incorporated into DNA or RNA in the place of the pyrimidine base. 5-fluorouracil, capecitabine, gemcitabine and decitabine are all common drugs in this category.

Folate Antagonists

• Folate antagonists block the activity of an enzyme called dihydrofolate reductase or DHFR, thereby halting the synthesis of tetrahydrofolate, a compound that cells need to synthesize purine and pyrimidine nucleotides. The goal is the same as with purine or pyrimidine antagonists, except that folate antagonists act on a different target to achieve a similar end effect. Methotrexate is the most commonly administered drug in this category.