Which drug is a classic antimetabolite used in leukemia treatment?

• A. Methotrexate
• B. Vincristine
• C. Daunorubicin
• D. Cyclophosphamide

Answer: (A)

Antimetabolites block DNA synthesis by mimicking normal cellular building blocks, hitting rapidly dividing leukemia cells hard. Methotrexate is a classic example of this drug class. It inhibits dihydrofolate reductase, which prevents formation of tetrahydrofolate and depletes the supply of thymidine and purines needed for DNA replication. This disruption slows or stops DNA synthesis, making it especially effective against fast-growing leukemic cells. In practice, methotrexate is used in various leukemia regimens, including central nervous system prophylaxis and high-dose therapy with leucovorin rescue to reduce toxicity.

Vincristine disrupts microtubule formation, causing mitotic arrest rather than interfering with nucleotide synthesis. Daunorubicin intercalates DNA and generates free radicals, not antimetabolite activity. Cyclophosphamide alkylates DNA, leading to cross-links. These different mechanisms explain why they aren’t classified as antimetabolites.