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Questions and Answers
The electrophilicity of nitrogen mustards is related to their ability to form?
What is an orally administered alkylating agent?
Temozolomide
The following structure modification leads to?
This reaction shows?
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Which chemical motif is responsible for oral bioavailability?
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Which chemical motif is responsible for targeting effect?
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Which structure is the main alkylator of DNA?
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This reaction results in?
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This structural modification leads to?
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This compound can cross the BBB and is used orally for treatment of brain tumors.
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Which chemical compounds are used as prophylactic against toxicity of acrolein?
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Comparing structure, A and B, which one is designed to have less affinity to CYP?
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Which structure corresponds to a chemoprotectant compound used in combination with cis-platinum complexes?
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Which of these is not a reversible proteasome inhibitor?
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In the body, via a sequence of reactions, capecitabine is converted into which molecule (drug)?
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The fluorine on fludarabine phosphate confers what type of activity (or property)?
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Which enzyme will very effectively phosphorylate this drug - Gemcitabine?
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This is the activated form of fluorouracil – which enzyme does it inhibit?
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What is the active form of the prodrug cyclophosphamide?
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Which enzyme is responsible for the first activation step of gemcitabine?
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This reaction is carried out by which enzyme?
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Pemetrexed has been used in several cancers beyond the leukemia/lymphoma types. Which enzyme does it preferentially inhibit?
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Nitrogen mustards react with DNA through the formation of which reactive intermediate?
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This drug better resembles which form of folic acid?
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Most modifications of the folic acid structure to make antifolates are made on which part of the molecule?
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Which of the following drugs is less prone to activation?
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Fluorouracil (when converted to active drug) could be very effective at inhibiting thymidylate synthase if combined with which of the following drugs?
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Which of these drugs will cause more extensive & less repairable DNA damage?
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Carboplatin is a platinum analog that has which of the properties below when compared to cis-platin?
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For which enzyme will this drug be more selective?
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The presence of the fluoride on fludarabine led to?
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Which one of the following is the reactive species generated from temozolomide?
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For mercaptopurine patients, genotype must be determined to avoid myelosuppression, which could result from low or deficiency of the following enzyme?
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Pemetrexed is a folate analog that shows what type of affinity to folyl polyglutamate synthesis as compared to Methotrexate?
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Which is true of crosslinking agents?
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Study Notes
Electrophilicity of Nitrogen Mustards
- Electrophilicity is linked to the formation of Aziridinium cation.
- Useful as alkylating agents due to their reactivity.
Orally Administered Alkylating Agents
- Certain agents can be administered orally, facilitating patient compliance.
Structure Modifications
- COOH group enhances stability of compounds.
- Modifications can increase selectivity and decrease cytotoxicity.
- Substituting CH3 with phenyl increases reactivity in nitrogen mustards.
- Some structural changes can result in fast-acting and low-toxicity compounds.
Reactions and Metabolism
- Reactions can deactivate alkylating agents or modify them to improve stability.
- The metabolism of alkylating agents is crucial for therapeutic effect.
Chemical Motifs
- Certain chemical structures contribute to oral bioavailability, targeting effect, and specific reactivity towards DNA.
Key Alkylators
- Specific structures are identified as main alkylators of DNA, critical for inhibiting cell division and overcoming cancer.
Cyclophosphamide
- Activation leads to toxic acrolein, which poses further health risks.
- Deactivation pathways can also yield toxic products.
Structural Modifications
- Alterations in structure can result in loss of activity or improved stability.
- Some modifications slow down metabolism, enhancing drug efficacy.
Brain Tumor Treatment
- Compounds capable of crossing the Blood-Brain Barrier (BBB) are utilized for treating brain tumors.
Prophylactic Compounds
- Certain chemical compounds serve as prophylactic agents against toxic effects, like those from acrolein.
CYP Affinity
- Comparison between structures can reveal which compounds are designed for reduced affinity to Cytochrome P450 enzymes.
Chemoprotectants
- Structure identification is essential for compounds used in conjunction with cis-platinum complexes for cancer treatment.
Proteasome Inhibitors
- Distinguishing between reversible and non-reversible proteasome inhibitors is key in targeting cancer.
Capecitabine Metabolism
- Converted to active drug through a sequence of reactions, critical for therapeutic applications.
Fludarabine Phosphate Activity
- The presence of fluorine confers resistance to deaminases, enhancing drug longevity and effectiveness.
Gemcitabine Activation
- Deoxycytidine kinase phosphorylates Gemcitabine effectively, enhancing its action against tumors.
Thymidylate Synthase Inhibition
- Active form of fluorouracil inhibits thymidylate synthase, a key enzyme in DNA synthesis.
Nitrogen Mustards Reactivity
- These compounds generate reactive intermediates that interact with DNA, leading to crosslinking.
Folate Analog Modifications
- Most modifications to create antifolates occur on specific parts of the folic acid structure for optimal activity.
Enzyme Affinities
- Understanding enzyme selectivity helps in designing effective therapeutics with reduced side effects.
Temozolomide's Reactive Species
- Identifying the reactive species from temozolomide is crucial for understanding its mode of action.
Mercaptopurine Genotyping
- Patients may require genotyping to prevent myelosuppression due to enzyme deficiencies.
Pemetrexed Affinity
- Pemetrexed shows higher affinity for folyl polyglutamate synthesis compared to Methotrexate, positioning it for enhanced therapeutic use.
Crosslinking Agents
- Just one cross-link can significantly damage DNA, inhibiting cell proliferation and establishing a therapeutic window for cancer treatment.
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Description
Test your knowledge on the electrophilicity of nitrogen mustards and their structural modifications. This quiz covers the effects of various groups on stability, selectivity, and reactivity of these alkylating agents. Perfect for students studying medicinal chemistry or pharmacology.
