Folic acid analogues

The term folic acid analogues refers to a group of substances that act as analogues of folic acid in DNA and RNA nucleotide synthesis.

Folic acid antagonists in the narrower sense are a small group of (non-selectively acting) cytostatic drugs (so-called antimetabolites) with methotrexate (MTX) as the lead substance. Methotrexate is a classic folic acid analogue, a false substrate (see formulae) for the enzyme dihydrofolic acid reductase (DHFR) whose function is thus inhibited. DHFR converts folic acid into the biologically important tetrahydrofolic acid. The resulting deficiency of tetrahydrofolic acid inhibits the synthesis of purine and thymidine, and subsequently the synthesis of DNA and RNA. In addition to the cytotoxic effects initiated by this, the folic acid antagonists and especially MTX have an immunosuppressive and antiphlogistic effect.

Folic acid antagonists (with cytostatic effect) include:

• Aminopterin
• Methotrexate
• Pemetrexed