Antimetabolite

The drug methotrexate (right) is an antimetabolite that interferes with the metabolism of folic acid (left).

An antimetabolite is a chemical that inhibits the use of a metabolite, which is another chemical that is part of normal metabolism.^[1] Such substances are often similar in structure to the metabolite that they interfere with, such as the antifolates that interfere with the use of folic acid. The presence of antimetabolites can have toxic effects on cells, such as halting cell growth and cell division, so these compounds are used as chemotherapy for cancer.^[2]

Function

Cancer treatment

Antimetabolites can be used in cancer treatment,^[3] as they interfere with DNA production and therefore cell division and the growth of tumors. Because cancer cells spend more time dividing than other cells, inhibiting cell division harms tumor cells more than other cells.

Anti-metabolites masquerade as a purine (azathioprine, mercaptopurine) or a pyrimidine, chemicals that become the building-blocks of DNA. They prevent these substances becoming incorporated in to DNA during the S phase (of the cell cycle), stopping normal development and division.^[4]

They also affect RNA synthesis. However, because thymidine is used in DNA but not in RNA (where uracil is used instead), inhibition of thymidine synthesis via thymidylate synthase selectively inhibits DNA synthesis over RNA synthesis.

Due to their efficiency, these drugs are the most widely used cytostatics.

In the ATC system, they are classified under L01B.

Antibiotics

Antimetabolites may also be antibiotics, such as sulfanilamide drugs, which inhibit dihydrofolate synthesis in bacteria by competing with para-aminobenzoic acid.^[5]

Types

Main categories of these drugs include:

• base analogs (altered nucleobases):
  • purine analogues
  • pyrimidine analogues
• nucleoside analogues:
  • nucleosides with altered nucleobases
  • nucleosides with altered sugar component (e.g. Cytarabine, ...)
• nucleotide analogues
• antifolates

See also

• Antinutrient

References

1. Smith, A. L. (1997). Oxford dictionary of biochemistry and molecular biology. Oxford [Oxfordshire]: Oxford University Press. p. 43. ISBN 0-19-854768-4.
2. Peters GJ, van der Wilt CL, van Moorsel CJ, Kroep JR, Bergman AM, Ackland SP (2000). "Basis for effective combination cancer chemotherapy with antimetabolites". Pharmacol. Ther. 87 (2–3): 227–53. doi:10.1016/S0163-7258(00)00086-3. PMID 11008002.
3. Antineoplastic Antimetabolites at the US National Library of Medicine Medical Subject Headings (MeSH)
4. Takimoto CH, Calvo E. "Principles of Oncologic Pharmacotherapy" in Pazdur R, Wagman LD, Camphausen KA, Hoskins WJ (Eds) Cancer Management: A Multidisciplinary Approach. 11 ed. 2008.
5. "The Organic Chemistry of Drug Design and Drug Action" (2nd edition), R. B. Silverman, 2004.

External links

• Overview at University of Nebraska