Mechanism of Action of Sulphonamides
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Questions and Answers

How does the amide group in sulfonamides affect their polarity?

The amide group lowers the polarity of sulfonamides, making them less ionisable.

What role do enzymes play in the metabolism of sulfonamide prodrugs?

Enzymes, such as peptidases, metabolize sulfonamide prodrugs to generate primary amines.

Identify a key clinical application of sulfonamides.

Sulfonamides are commonly used to treat urinary tract infections.

What is the significance of R2 in sulfanilamide analogues?

<p>R2's variability affects plasma protein binding, solubility, and overall pharmacokinetics.</p> Signup and view all the answers

How do sulfonamides differ in effectiveness compared to penicillins?

<p>Sulfonamides were the antibacterial drugs of choice before penicillins became available.</p> Signup and view all the answers

What advantage do alkyl groups provide to sulfonamide prodrugs?

<p>Alkyl groups increase the hydrophobic character, facilitating easier gut wall crossing.</p> Signup and view all the answers

What enzyme do sulphonamides competitively inhibit and why is this target significant?

<p>Sulphonamides inhibit dihydropteroate synthetase, which is significant because it is crucial for synthesizing the tetrahydrofolate cofactor needed for DNA biosynthesis.</p> Signup and view all the answers

Explain how sulphonamides mimic para-aminobenzoic acid (PABA) in their mechanism of action.

<p>Sulphonamides mimic the structure of PABA, allowing them to bind to the active site of dihydropteroate synthetase and block the enzyme's action.</p> Signup and view all the answers

Why are sulphonamides considered bacteriostatic agents rather than bactericidal?

<p>Sulphonamides are bacteriostatic because they inhibit bacterial growth and reproduction rather than killing the bacteria outright.</p> Signup and view all the answers

Describe the metabolic process that sulphonamides undergo and its implications.

<p>Sulphonamides undergo N-acetylation, which increases their hydrophobicity and reduces aqueous solubility, potentially leading to toxic side effects.</p> Signup and view all the answers

Identify the main reason why sulphonamides may not be ideal for patients with weakened immune systems.

<p>Sulphonamides may not be ideal for such patients because they are bacteriostatic and may not effectively control bacterial infections in immunocompromised individuals.</p> Signup and view all the answers

What distinguishes the presence of dihydropteroate synthetase in bacterial cells from human cells?

<p>Dihydropteroate synthetase is present only in bacterial cells and not in human cells, making it a selective target for sulphonamides.</p> Signup and view all the answers

Discuss the impact of resistant bacterial strains on the efficacy of sulphonamides.

<p>Resistant strains can produce additional PABA, which competes with sulphonamides for the active site of dihydropteroate synthetase, thereby reducing the drug's effectiveness.</p> Signup and view all the answers

Why might sulphonamides not be utilized as prodrugs for gut infections?

<p>Sulphonamides are not typically designed as prodrugs for gut infections because their mechanism relies on inhibiting a specific enzyme not present in human cells.</p> Signup and view all the answers

What is the significance of the primary amino group in the structure of sulphonamides?

<p>The primary amino group is essential for the antibacterial activity of sulphonamides as it is crucial for their mechanism of action.</p> Signup and view all the answers

How does Prontosil function as a prodrug in the treatment of infections?

<p>Prontosil is metabolized in vivo to sulfanilamide, which is the active sulphonamide that exhibits antibacterial properties.</p> Signup and view all the answers

What role does the aromatic ring play in the structure-activity relationships of sulphonamides?

<p>The aromatic ring is essential for the activity of sulphonamides, as it contributes to their binding affinity and overall antibacterial action.</p> Signup and view all the answers

Why must the sulphonamide nitrogen be primary or secondary for effective antibacterial activity?

<p>The primary or secondary nature of the sulphonamide nitrogen is necessary for the drug's interaction with bacterial targets, enabling its antibacterial effects.</p> Signup and view all the answers

Discuss the clinical application of sulfanilamide as a synthetic antibacterial agent.

<p>Sulfanilamide is clinically applied in treating a wide range of bacterial infections, establishing it as the first synthetic antibacterial agent.</p> Signup and view all the answers

What is the mechanism of action by which sulphonamides exert their antibacterial effect?

<p>Sulphonamides inhibit bacterial folate synthesis by mimicking para-aminobenzoic acid (PABA), thereby blocking the production of folic acid.</p> Signup and view all the answers

Explain the concept of prodrugs in the context of sulphonamides and gut infections.

<p>Prodrugs like Prontosil are inactive until metabolized, allowing them to effectively deliver active sulphonamides to combat gut infections.</p> Signup and view all the answers

How does para-substitution on the sulphonamide structure affect its activity?

<p>Para-substitution is essential for the activity of sulphonamides, as it optimizes their interaction with target enzymes in bacteria.</p> Signup and view all the answers

Study Notes

Mechanism of Action

  • Dihydropteroate synthetase is a bacterial enzyme absent in human cells.
  • Plays a vital role in the biosynthesis of tetrahydrofolate cofactor, crucial for pyrimidine and DNA biosynthesis.
  • Essential for cell growth and division.

Sulphonamides

  • Act as competitive enzyme inhibitors and are classified as bacteriostatic agents.
  • Not recommended for immunocompromised patients due to reduced efficacy.
  • Mimic substrate para-aminobenzoic acid (PABA) to bind at the active site, inhibiting its access.
  • Inhibition is reversible, with resistance sometimes resulting from strains producing excess PABA.

Binding Interactions

  • Binding involves hydrogen bonds, van der Waals interactions, and ionic bonds at the active site of the enzyme.

Metabolic Differences

  • Dihydropteroate synthetase exists exclusively in bacterial cells.
  • Transport protein for folic acid is only found in mammalian cells.

Sulphonamides - Drug Metabolism

  • Metabolized primarily through N-acetylation, which increases hydrophobicity and decreases aqueous solubility.
  • This metabolic change can cause toxic side effects due to the formation of insoluble metabolites.

Prodrugs of Sulphonamides

  • Amide groups reduce polarity and prevent ionization, enhancing gut wall absorption.
  • Alkyl groups confer increased hydrophobicity, facilitating metabolism by enzymes (e.g., peptidases) and leading to active primary amines.
  • The ionized primary amine can form ionic interactions and acts as a strong hydrogen bond donor.

Sulphanilamide Analogues

  • Structure involves variations of aromatic and heteroaromatic rings (R2).
  • Structural differences affect plasma protein binding, blood levels, solubility, and pharmacokinetics; pharmacodynamics remain unchanged.

Applications of Sulphanilamides

  • Historically used as the main antibacterial agents before the advent of penicillins in the 1930s.
  • Current applications include treatment of urinary tract infections, eye lotions, gut infections, and mucous membrane infections.

Lead Compound

  • Prontosil, a red dye, was identified as having antibacterial activity in vivo but was inactive in vitro.
  • Metabolized into the active sulphonamide, establishing its role as a prodrug.
  • Sulphanilamide became the first synthetic antibacterial agent effective against a variety of infections.

Structure-Activity Relationships

  • The primary amino group (R1=H) is critical for activity.
  • Amide groups can also be present (R1=acyl), leading to prodrug forms that are inactive until metabolized.
  • The presence of an aromatic ring and para-substitution of the sulphonamide group is essential for activity, along with the nitrogen being primary or secondary in structure.

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Sulfonamides _ Sulphones.ppt

Description

This quiz explores the mechanism of action of sulphonamides, specifically focusing on dihydropteroate synthetase, an important bacterial enzyme. It examines how these competitive enzyme inhibitors interfere with bacterial growth by mimicking para-aminobenzoic acid. Understanding this mechanism is crucial for studying antifolate therapy in bacterial infections.

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