Anticancer Drugs - Part II: Antimetabolites
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What is the primary mechanism by which antimetabolites function?

  • They act as false substrates for nucleotide biosynthesis enzymes (correct)
  • They directly cause DNA damage
  • They inhibit protein synthesis
  • They enhance the synthesis of cellular metabolites

    • Which class of nucleotide do purine antagonists specifically inhibit?

  • Cytidine and Uridine
  • ADP and GDP
  • ATP and GTP
  • AMP and GMP (correct)

    • What significant side effect is associated with the use of mercaptopurine?

  • Severe diarrhea
  • Uric acid toxicity (correct)
  • Liver damage
  • Nausea and vomiting

    • How does allopurinol affect the efficacy of mercaptopurine?

    <p>It increases the levels of active 6-thioinosinic acid</p> Signup and view all the answers

    Mercaptopurine is classified as what type of agent?

    <p>An immunosuppressive agent</p> Signup and view all the answers

    What is the role of hypoxanthine-guanine phosphoribosyl-transferase (HPGRT) in relation to mercaptopurine?

    <p>It converts mercaptopurine to an active form</p> Signup and view all the answers

    In which condition is mercaptopurine primarily used?

    <p>Acute leukemia</p> Signup and view all the answers

    Which of the following statements about mercaptopurine is false?

    <p>It competes with uric acid for renal excretion</p> Signup and view all the answers

    What is the primary action of Vinca Alkaloids in the treatment of cancer?

    <p>Inhibit polymerization of microtubules</p> Signup and view all the answers

    Which characteristic of Estramustine phosphate (EMP) distinguishes it from its parent compound estramustine?

    <p>EMP is a prodrug with estrogenic effects</p> Signup and view all the answers

    Why is Estramustine phosphate not used to treat estrogen-dependent tumors?

    <p>It selectively targets prostate tissue</p> Signup and view all the answers

    What effect does Paclitaxel have on the microtubules during tumor treatment?

    <p>It stabilizes microtubules and prevents their breakdown</p> Signup and view all the answers

    What type of drug is Estramustine phosphate (EMP) described as?

    <p>A dual agent with cytostatic and hormonal effects</p> Signup and view all the answers

    What mechanism leads to the effectiveness of EMP against prostate cancer?

    <p>Disassociation of MAP-4 from microtubules</p> Signup and view all the answers

    Which of the following is a common side effect associated with Estramustine phosphate?

    <p>Pulmonary embolism</p> Signup and view all the answers

    Which statement correctly describes the pharmacological profile of Estramustine phosphate?

    <p>Its phosphate ester enhances water solubility and IV administration</p> Signup and view all the answers

    What is azathioprine primarily used for?

    <p>Immunosuppression in organ transplantation and autoimmune diseases</p> Signup and view all the answers

    How is azathioprine converted to 6-mercaptopurine?

    <p>By being attacked by glutathione</p> Signup and view all the answers

    What is the role of thymidylate synthase in pyrimidine metabolism?

    <p>It is the rate-limiting enzyme in dTMP synthesis</p> Signup and view all the answers

    What is the impact of the electron-withdrawing ability of the heterocyclic group on azathioprine?

    <p>It accelerates the conversion to mercaptopurine</p> Signup and view all the answers

    Which of the following drugs is metabolized by dihydropyrimidine dehydrogenase (DPD)?

    <p>5-Fluorouracil</p> Signup and view all the answers

    What is the significance of replacing the fluorine atom in 5-fluorouracil with an ethinyl moiety?

    <p>It enhances drug stability and therapeutic index</p> Signup and view all the answers

    Which statement accurately describes thioguanine?

    <p>It is ineffective when combined with allopurinol</p> Signup and view all the answers

    What adverse effect is associated with inhibiting thymidylate synthase in rapidly dividing cells?

    <p>Thymineless death</p> Signup and view all the answers

    What is the major use-limiting side effect of anthracyclines?

    <p>Cardiac toxicity</p> Signup and view all the answers

    How does Dexrazoxane function in the context of anthracycline treatment?

    <p>Decreases the cardiac toxicity by chelating iron</p> Signup and view all the answers

    What mechanism does Mitomycin C utilize to exert its effects?

    <p>Bioreductive alkylation</p> Signup and view all the answers

    What advantage does the enhanced stability of the quinone ring in Mitoxantrone provide?

    <p>Decreased production of highly toxic hydroxyl radicals</p> Signup and view all the answers

    Which cancer treatments is Mitoxantrone commonly used for?

    <p>Hormone-refractory prostate cancer and acute non-lymphocytic leukemia</p> Signup and view all the answers

    Which cancers is 5-fluorouracil (5-FU) primarily used to treat palliatively?

    <p>Colorectal, Breast, Stomach, and Pancreatic</p> Signup and view all the answers

    What is the primary mechanism by which 5-fluorouracil exerts its anticancer effect?

    <p>Acting as a competitive inhibitor of thymidylate synthetase</p> Signup and view all the answers

    What is the result of dihydropyrimidine dehydrogenase (DPD) metabolism of 5-fluorouracil?

    <p>Formation of neurotoxic 5-fluoro-5,6-dihydrouracil</p> Signup and view all the answers

    Which of the following improves the therapeutic index of 5-fluorouracil?

    <p>5-ethynyluracil</p> Signup and view all the answers

    What is the primary role of Tegafur in cancer treatment?

    <p>It is a prodrug converted into 5-fluorouracil.</p> Signup and view all the answers

    How does capecitabine function in the body?

    <p>It is absorbed intact and rapidly converted to 5-FU.</p> Signup and view all the answers

    What is the mechanism of action for Methotrexate as a folic acid antagonist?

    <p>It competes with dihydrofolic acid for dihydrofolate reductase.</p> Signup and view all the answers

    What effect does the inhibition of dihydrofolate reductase (DHFR) have on thymidylate synthase?

    <p>It causes a decrease in dihydrofolate levels and feedback inhibition of thymidylate synthase.</p> Signup and view all the answers

    What is the primary mechanism of action of Nelarabine in cancer treatment?

    <p>Inhibiting ribonucleotide reductase and DNA synthesis</p> Signup and view all the answers

    Which of the following anticancer agents is indicated for treating hairy cell leukemia?

    <p>Cladribine</p> Signup and view all the answers

    Which agent is known to inhibit ribonucleotide reductase by chelation with Fe2+?

    <p>Hydroxyurea</p> Signup and view all the answers

    What characteristic of Cladribine, Clofarabine, and Fludarabine makes them resistant to deamination by adenosine deaminase?

    <p>C2 halogen substitution</p> Signup and view all the answers

    What is the role of tubulin during mitosis?

    <p>To form microtubules for chromosome segregation</p> Signup and view all the answers

    Which anticancer drug is known to cause chain termination during DNA synthesis?

    <p>Nelarabine</p> Signup and view all the answers

    For which type of cancer is Fludarabine primarily used?

    <p>Chronic lymphocytic leukemia</p> Signup and view all the answers

    What is a significant property of Clofarabine that enhances its stability?

    <p>The presence of an arabinose fluorine group</p> Signup and view all the answers

    Study Notes

    Anticancer Drugs - Part II

    • Antimetabolites: These compounds prevent normal cellular metabolism or biosynthesis. They are structurally similar to normal metabolites, acting as antagonists. Classified by the nucleotide they inhibit.

    Types of Antimetabolites

    • Purine Antagonists: Inhibit purine-based nucleotides like AMP and GMP. 6-Mercaptopurine (6-MP) is an example.

    • Pyrimidine Antagonists: Inhibit pyrimidine-based nucleotides like dTMP. Examples include 5-fluorouracil (5-FU) and related drugs.

      • 5-FU: Metabolized into an active form that inhibits thymidylate synthetase.

    • DNA Polymerase Inhibitors: Directly or indirectly inhibit DNA polymerase. Examples include cytarabine (ara-C).

    • Folate Antagonists: These inhibit the synthesis of the cofactor for thymidylate synthesis. Examples include methotrexate.

    Specific Antimetabolites

    • 6-Mercaptopurine (6-MP): A prodrug converted in the body to a potent inhibitor of purine synthesis. Used to treat acute leukemia and pediatric lymphoma. It's important to understand the drug's metabolic pathway and potential side effect, especially uric acid toxicity.

    • Azathioprine: An imidazolyl derivative that is a prodrug of 6-MP. It's valuable because it provides a more sustained activity compared to 6-MP, slowing conversion to active drug. Used in organ transplantation and autoimmune diseases

    • Thioguanine: Administered orally, inhibiting the synthesis of purine nucleotides. Used in treating certain leukemias, particularly important when combined with other drugs like cytarabine.

    • Cytarabine (ara-C): A pyrimidine analog that is effective against leukemia. Important for understanding its conversion to triphosphate and subsequent miscoding effects that inhibit chain elongation in DNA & RNA synthesis

    • Gemcitabine: Another pyrimidine analog, also used in various cancers, such as breast, pancreatic and non-small cell lung cancers. Important aspects are its conversion to triphosphate analogue and its effects on DNA/RNA synthesis and cell death.

    • Nelarabine: A prodrug that is converted to an active form that inhibits ribonucleotide reductase (RNR) and DNA synthesis by chain termination. It increased water solubility is important.

    • Cladribine, Clofarabine, Fludarabine: These are 2-haloadenosine analogs designed to be resistant to deamination by adenosine deaminase. Used in specific cancers.

    • 5-Fluorouracil (5-FU): A pyrimidine analog used in many cancers. Is metabolized by dihydropyrimidine dehydrogenase (DPD) into an inactive form, but this metabolic step can be improved via 5-ethynyluracil which improves therapeutic index

    • Fluoxuridine: Converted into active form 5-FdUMP, inhibiting thymidylate synthetase.

    • Hydroxyurea: Inhibits ribonucleotide reductase, disrupting DNA synthesis and decreasing the level of deoxyribonucleotides. Used in melanoma and ovarian cancer.

    Antimitotic Agents

    • Vinca Alkaloids (Vinblastine, Vincristine): Inhibit microtubule polymerization, interfering with mitosis. Important in various lymphomas and leukemias.

    • Estramustine Phosphate: A dual cytostatic and hormonal agent; it acts on both mitotic and hormone pathways.

    • Taxanes (Paclitaxel, Docetaxel): Stabilize microtubules, inhibiting depolymerization, which interferes with mitotic spindle formation preventing cell division.

    • Mitoxantrone: An anthracenedione that intercalates with DNA and interferes with topoisomerase II preventing DNA and RNA synthesis

    • Mitomycins: Act by bioreductive alkylation of DNA. Interfere with cell division.

    Other

    • Anthracyclines (Doxorubicin, Daunorubicin, Idarubicin): Intercalate with DNA, causing single and double-strand breaks. Important consideration is the role of iron and its contribution to the drug's cardiotoxicity and the role of Dexrazoxane.

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    Anticancer Drugs Part II 2024 PDF

    Description

    This quiz delves into the second part of anticancer drugs focusing on antimetabolites. Learn about their classifications, including purine and pyrimidine antagonists, DNA polymerase inhibitors, and folate antagonists. Test your understanding of specific drugs like 6-Mercaptopurine and 5-Fluorouracil.

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