Leoni NSAID medchem

    Cards (62)

    • What are the learning outcomes for Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in PHA-6020Y?
      • Recap of the COX pathway
      • Know that NSAIDs inhibit all three branches of the COX pathway
      • Describe the relationship between aspirin receptor site and the COX active site
      • Understand aspirin’s mechanism of action
      • Awareness of alternatives to aspirin as antiplatelet drugs that inhibit COX active site
      • Apply medicinal chemistry knowledge to design selective COX inhibitors
    • Which three branches of the COX pathway are affected by NSAIDs?
      Thromboxane, prostacyclin, and the prostaglandins
    • What is the relationship between the aspirin receptor site and the COX active site?
      Aspirin binds irreversibly to the aspirin receptor site, blocking arachidonic acid access to the COX active site
    • What is aspirin’s mechanism of action?
      Aspirin irreversibly blocks the COX active site by binding to a serine residue, preventing arachidonic acid from accessing the enzyme
    • What are the alternatives to aspirin as antiplatelet drugs that competitively inhibit the COX active site?
      • Other salicylates
      • Ibuprofen
    • How can medicinal chemistry knowledge be applied for the design of inhibitors suitable to selectively fit the COX family of proteins?
      By tailoring chemical interactions and steric requirements to fit specific COX isoforms
    • What is the COX pathway also known as?
      Prostaglandin synthase pathway
    • What molecule fits into the active site of the cyclooxygenase enzyme Cox to access the prostaglandin?
      Arachidonic acid
    • What is the first prostaglandin produced in the COX pathway?
      Prostaglandin G2
    • What is prostaglandin G2 converted to in the COX pathway?
      Prostaglandin H2
    • Which prostaglandin is produced by the conversion of prostaglandin H2?
      Prostaglandin D2
    • What is prostaglandin E2 also known as?
      PGE2
    • What is prostaglandin F2α also known as?
      PGF2α
    • What enzyme converts prostaglandin H2 to thromboxane A2?
      Thromboxane synthase
    • What is the product of thromboxane synthase in the COX pathway?
      Thromboxane A2
    • What are the effects of prostaglandins on the body?
      Prostaglandins cause inflammatory responses, swelling, inflammation, pain, and fever
    • What is the function of platelet aggregation inducers?
      Platelet aggregation inducers stimulate the clumping together of platelets
    • What is the function of platelet aggregation inhibitors?
      Platelet aggregation inhibitors prevent platelets from clumping together
    • Where are phospholipids primarily located in cells?
      In the cell membrane
    • What is produced from the degradation of cell membrane phospholipids?
      Arachidonic acid
    • What enzyme does arachidonic acid bind to in the COX pathway?
      Cyclooxygenase enzyme Cox
    • What are the physiological effects of prostaglandins?
      • Inflammatory
      • Cause swelling
      • Cause inflammation
      • Cause pain
      • Cause fever
    • At what physiological pH is aspirin deprotonated?

      At physiological pH
    • What reference is given for COX inhibition?
      N Engl J Med, 2001, 345, 1809
    • How does the hydroxyl group on serine residues facilitate aspirin's transesterification?
      • The hydroxyl group facilitates the transesterification of aspirin's acyl group
      • It attacks the electrophilic carbonyl carbon of aspirin
    • How does the carboxylate anion of aspirin facilitate its transesterification with serine residues?
      • Removes proton on serine
      • Makes oxygen more nucleophilic
      • Increases serine's ability to attack the carbonyl group
    • Which amino acid residue forms a hydrogen bond with the carbonyl group on aspirin?
      Tyrosine residue 385
    • Why is aspirin’s inhibition of COX considered irreversible?
      • A covalent bond is formed between aspirin and serine residues
      • It cannot be easily reversed without the synthesis of new COX enzymes
    • What type of protein is COX?
      COX is a homo dimer protein containing two identical polypeptide chains
    • What feature allows arachidonic acid to enter the COX active site?
      A hydrophobic channel leading to the active site
    • What moiety constitutes the active site of COX enzymes?
      A heme moiety
    • How does aspirin inhibit COX without competing for the active site?
      Aspirin irreversibly binds to a serine residue, preventing arachidonic acid from reaching the heme active site
    • To which serine residue is the acyl group of aspirin transferred?
      Serine 529
    • How does acylated serine 529 affect access to the COX active sites?
      It blocks the access to the enzyme active sites, preventing arachidonic acid from binding to the heme moiety
    • How do non-selective NSAIDs like ibuprofen inhibit COX?
      They act as competitive inhibitors of both COX-1 and COX-2 enzymes
    • What is the chemical name for aspirin?
      Acetylsalicylic acid (ASA)
    • Is aspirin selective for COX-1 or COX-2 enzymes?
      No, it is non-selective for COX-1 and COX-2 enzymes
    • To which residue do non-selective NSAIDs bind?
      Arg120
    • What type of interaction do non-selective NSAIDs form with Arg120?
      Ionic interaction
    • Are non-selective NSAIDs competitive or irreversible inhibitors of COX-1 and COX-2?
      Competitive inhibitors of both COX-1 and COX-2