Etoposide-TopIIα Binding Interactions Quiz
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Questions and Answers

What nucleophiles can the aziridinium ion react with?

  • SH, OH, and NH groups only
  • Water only
  • DNA only
  • Unpaired DNA and/or cell nucleophiles such as SH, OH, and NH groups (correct)

    • How does an aromatic nitrogen substituent R, like phenyl, stabilize the aziridinium ion?

  • By forming inactive dehalogenated diol
  • By destabilizing the lone pair of electrons
  • Through resonance and stabilizing the lone pair of electrons (correct)
  • By increasing its reactivity

    • How does resonance delocalization affect the rate of intramolecular nucleophilic attack?

  • It significantly slows the rate (correct)
  • It stops the reaction completely
  • It has no impact on the rate
  • It accelerates the rate

    • What can act as nucleophiles to advance the degradative process in aqueous media?

    <p>Both mustard nitrogen and oxygen of water</p> Signup and view all the answers

    How can the decomposition reactions of nitrogen mustards be inhibited?

    <p>By protonation to eliminate nucleophilic character</p> Signup and view all the answers

    Which factor helps enhance stability in aqueous solution for nitrogen mustards?

    <p>Acidic pH (e.g., 3-5)</p> Signup and view all the answers

    What is a characteristic feature of Chlorambucil among aromatic nitrogen mustards?

    <p>Resonance-stabilized amine structure</p> Signup and view all the answers

    Which phase of the cell cycle do epipodophyllotoxins have the most devastating impact on?

    <p>S phase</p> Signup and view all the answers

    What is a common mechanism of resistance to epipodophyllotoxins?

    <p>Enhanced DNA repair mechanisms</p> Signup and view all the answers

    How is a water-soluble phosphate ester analogue of etoposide administered?

    <p>In aqueous vehicles</p> Signup and view all the answers

    What is the major metabolite generated by lactone hydrolysis of etoposide and teniposide?

    <p>Inactive hydroxy acid</p> Signup and view all the answers

    Which enzyme catalyzes the O-demethylation of epipodophyllotoxins?

    <p>CYP3A4</p> Signup and view all the answers

    What is the purpose of glucuronide or sulfate conjugation in the metabolism of epipodophyllotoxins?

    <p>Inactivation and excretion of metabolites</p> Signup and view all the answers

    What is an isoform where etoposide was found in a ternary complex according to the text?

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

    How is the area that binds the glycoside moiety of epipodophyllotoxins described according to the text?

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

    Which protein mediates compromised carrier-mediated cellular transport of cisplatin?

    <p>CTR1</p> Signup and view all the answers

    What is one of the mechanisms of resistance to cisplatin therapy mentioned in the text?

    <p>Uncontrolled expression of noncoding RNA (lncRNA)</p> Signup and view all the answers

    Which proteins are responsible for cellular efflux in cisplatin-resistant tumors?

    <p>P-type ATP 7A/7B and multidrug resistance proteins</p> Signup and view all the answers

    What cellular process can lead to increased DNA repair and/or tolerance to cisplatin-induced DNA damage?

    <p>Uncontrolled expression of noncoding RNA (lncRNA)</p> Signup and view all the answers

    Which repair proteins remove platinum-damaged segments from DNA in cisplatin-resistant tumors?

    <p>Mismatch repair proteins</p> Signup and view all the answers

    What interaction reduces the number of drug-DNA adducts when amifostine is activated?

    <p>Interaction with cisplatin</p> Signup and view all the answers

    Which mechanism contributes to acquired resistance after multiple courses of cisplatin therapy in ovarian cancer?

    <p>Uncontrolled expression of noncoding RNA (lncRNA)</p> Signup and view all the answers

    What is a mechanism that leads to enhanced intracellular inactivation of cisplatin?

    <p>Vesicle drug trapping</p> Signup and view all the answers

    What is the mechanism for testosterone reduction to DHT?

    <p>Hydrogen transfer from NADPH to the 5α-position of testosterone</p> Signup and view all the answers

    Which enzyme is responsible for the conversion of testosterone into DHT?

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

    What are finasteride and dutasteride known as?

    <p>5α-reductase inhibitors</p> Signup and view all the answers

    Which inhibitor is a selective inhibitor of 5AR2?

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

    What happens when 5AR2 is inhibited with finasteride or dutasteride?

    <p>Decreases in plasma and intraprostatic DHT concentrations</p> Signup and view all the answers

    What do finasteride and dutasteride have the ability to do, besides being competitive inhibitors of 5α-reductase?

    <p>Inactivate 5AR through irreversible modification of the enzyme</p> Signup and view all the answers

    What does the inhibition constant (IC50) for finasteride suggest?

    <p>Finasteride is more potent as an inhibitor of 5AR2 than 5AR1</p> Signup and view all the answers

    How do finasteride and dutasteride mimic the pathway of testosterone reduction to 5α-dihydrotestosterone?

    <p>By binding to the same site on 5α-reductase where testosterone binds</p> Signup and view all the answers

    What is the primary metabolic pathway of finasteride in the liver?

    <p>Formation of a monocarboxylic acid from monohydroxylation of the t-butyl side chain</p> Signup and view all the answers

    What role do lipophilic groups at the 17β position play in improving the biological activity of finasteride?

    <p>Improving its biological activity</p> Signup and view all the answers

    How does finasteride's mechanism-based inhibition explain its potency and specificity in treating benign prostatic hyperplasia?

    <p>By forming an enzyme-bound dihydrofinasteride-NADP adduct</p> Signup and view all the answers

    What does dutasteride's inhibition of 5AR2 compared to 5AR1 imply?

    <p>Dutasteride is less potent as an inhibitor of 5AR2 than 5AR1</p> Signup and view all the answers

    What prevents enol tautomerization to a keto group in finasteride?

    <p>4-aza functional group</p> Signup and view all the answers

    What is formed when finasteride accepts a H- transfer from NADPH to the 1α-position of its A-ring?

    <p>$\text{Enol intermediate}$</p> Signup and view all the answers

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