Which of the following antineoplastic and immunosuppressant drugs is a dihydrofolate reductase inhibitor ?
Dihydrofolate reductase is an enzyme involved in folate metabolism. Inhibiting it blocks the production of tetrahydrofolate, which is necessary for DNA synthesis. So, drugs that inhibit DHFR are typically used in cancer and immunosuppression because they interfere with cell proliferation.
Trimethoprim is a common DHFR inhibitor, but wait, that's for bacterial infections. However, in the context of cancer, methotrexate comes to mind. Methotrexate is a folate antagonist and a DHFR inhibitor. It's used in chemotherapy and for autoimmune diseases. So, methotrexate would be the correct answer here.
Now, looking at the options. Let's say the options are A. Methotrexate, B. Cyclophosphamide, C. Azathioprine, D. Vincristine. The correct answer is A. Methotrexate.
Why are the others wrong? Cyclophosphamide is an alkylating agent. Azathioprine is a purine analog, inhibits purine synthesis. Vincristine is a microtubule inhibitor. Trimethoprim isn't listed here, but methotrexate is the key one in this category for the question's context.
Clinical pearl: Remember that methotrexate's DHFR inhibition leads to folate deficiency, so leucovorin is used as a rescue agent. High-yield fact for exams.
**Core Concept**
Dihydrofolate reductase (DHFR) inhibition disrupts tetrahydrofolate synthesis, a cofactor required for purine and thymidylate synthesis. This mechanism is exploited in antineoplastic and immunosuppressant drugs to inhibit rapidly dividing cells.
**Why the Correct Answer is Right**
Methotrexate is a classic DHFR inhibitor. It competitively binds DHFR, blocking the reduction of dihydrofolate to tetrahydrofolate. This depletes folate derivatives essential for DNA/RNA synthesis, making it effective in cancers (e.g., leukemia) and autoimmune diseases. Its immunosuppressive effect arises from suppressing lymphocyte proliferation.
**Why Each Wrong Option is Incorrect**
**Option B:** Cyclophosphamide is an alkylating agent that crosslinks DNA, not a DHFR inhibitor.
**Option C:** Azathioprine inhibits purine synthesis via inosine monophosphate dehydrogenase, not DHFR.
**Option D:** Vincristine binds tubulin, inhibiting microtubule formation, unrelated to folate metabolism.
**Clinical Pearl / High-Yield Fact**
Methotrexate toxicity (e.g., myelosuppression, mucositis) is mitigated with leucovorin rescue, which bypasses DHFR inhibition to replenish folate. Remember: "Methotrexate = DHFR inhibitor + folate antagonist."
**Correct Answer: A. Methotrexate**