Untitled

Penicillin Breakthrough

Table of Contents

  • History

  • Mechanism of Action

  • Pharmacophore

  • Penicillin Analogues

  • Structure and its Improvement

  • Chemical Structures of Penicillin

  • Classification

01 HISTORY OF PENICILLIN

  • Dr. Alexander Fleming's Quote:

    • "One sometimes finds what one is not looking for. When I woke up just after dawn on Sept. 28, 1928, I certainly didn’t plan to revolutionize all medicine by discovering the world's first antibiotic, or bacteria killer. But I guess that's exactly what I did."

Discovery of Penicillin

  • Key Events in 1928:

    • Observation: Dr. Fleming returned from vacation and noticed a mold called Penicillium notatum on a Staphylococcus bacteria Petri dish.

      • Mold inhibited the growth of nearby bacteria.

    • Findings:

      • Identified self-defence chemical with antibacterial properties.

      • Named the substance penicillin.

    • Continuation of Research:

      • Howard Florey and Ernst Chain from the University of Oxford completed the research initiated by Fleming.

Penicillin Overview

  • Nature of Penicillin:

    • Antibiotics derived from the fungus Penicillium.

    • One of the most important discoveries in medicine.

    • Chemical Structure:

      • Includes a thiazolidine ring connected to a beta-lactam ring essential for antibacterial activity.

    • Classification:

      • Natural Penicillin, Aminopenicillin, Antistaphylococcal Penicillins, Extended-Spectrum Penicillin, Beta-Lactamase Inhibitor.

Penicillin Uses and Target

  • Medical Uses:

    • Treats various bacterial infections (respiratory, skin, urinary tract, pneumonia, meningitis).

  • Mechanism:

    • Interferes with the synthesis of bacterial cell walls, which do not affect human cells (lack of cell wall).

02 MECHANISM OF ACTION PENICILLIN

  • Antibiotic Action Mechanisms:

    • Types:

      • Disruption of cell membrane function

      • Inhibition of cell wall synthesis

      • Inhibition of nucleic acid synthesis

      • Inhibition of protein synthesis

Penicillin Binding

  • Binding Action:

    • Penicillin binds to Penicillin-Binding Proteins (PBP) on the cell wall of susceptible bacteria.

      • Inhibits transpeptidation and prevents peptidoglycan synthesis.

      • Leads to bacterial cell death through autolysis.

03 CLASSIFICATION OF PENICILLIN

  • Classification Criteria:

    • Based on Source

    • Route of Administration

    • Spectrum of Activity

    • Resistance to Acid and Enzymes

Examples

  • Natural Penicillin:

    • Penicillin G, Penicillin V

  • Semisynthetic Penicillin:

    • Ampicillin, Methicillin

  • Extended-Spectrum Penicillin:

    • Carbenicillin, Piperacillin

04 STRUCTURE-ACTIVITY RELATIONSHIP OF PENICILLIN

Key Structural Components

  • β-lactam Ring:

    • Essential for antibacterial activity; any disruption leads to loss of function.

    • Susceptible to hydrolysis by bacterial enzymes, disrupting cell wall synthesis.

  • Thiazolidine Ring:

    • Contributes to molecular stability.

    • Modifications affect stability and absorption.

  • Side Chain (R Group):

    • Influences spectrum of activity and susceptibility to bacterial enzymes.

Substitution on Thiazolidine Ring

  • Positions:

    • Position-1: Oxidation of sulfur improves acid stability but reduces activity.

    • Position-2: No substitutions allowed.

    • Position-3: Carboxylic acid required for activity, altering this reduces effects.

    • Position-4: Nitrogen required; substitutions reduce activity.

    • Position-5: Unsubstituted necessary to maintain chirality and cis-formation.

Substitution on Lactam Ring

  • Position-6:

    • Adding R-group increases activity.

  • Position-7:

    • Carbonyl on beta-lactam ring is essential.

05 PHARMACOPHORE PENICILLIN

Structure of Various Penicillins

  • Examples Include:

    • Penicillin G, Penicillin V, Ampicillin, Amoxicillin, Methicillin.

Activity Relation

  • Structures share core elements essential for antibacterial properties while varying in side chains to modify pharmacological effects.

06 PENICILLIN ANALOGUES

  • Categories:

    • Natural Penicillin

    • Antistaphylococcal Penicillin

    • Aminopenicillin

Notable Analogues Include:

  • Natural:

    • Penicillin G

    • Penicillin V

  • Antistaphylococcal:

    • Methicillin, Oxacillin

  • Aminopenicillin:

    • Amoxicillin

Questions Section

  1. What determines the antibacterial spectrum and pharmacological properties?

  2. What do all penicillins compose with their side chain?

  3. How do beta-lactam antibiotics work on bacteria?

Answers Section

  1. Side Chain

  2. B-lactam and Thiazolidine ring

  3. Inhibit cell wall synthesis, results in lysis of bacteria.

References

  • Akhavan BJ, Khanna NR, Vijhani P. Amoxicillin. [Updated 2023 Nov 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482250/

Credits

  • Presentation template created by Slidesgo

  • Icons by Flaticon

  • Infographics & images by Freepik