Description
•History & Introduction
•Commercial Production of antibiotics
•Over view of Mechanism of action of various antibiotics
•Various methods of Classification of Antibiotics
• Understand the history of evolution of antibiotics as therapeutic agents
• Define the term “antibiotic”
• Explain how antibiotics are commercially produced
• Explain the general mode of action of various antibiotics
• Classify antibiotics based on various criteria
Antibiotics
• Historical background,
• Nomenclature,
• Stereochemistry,
• Structure activity relationship,
• Chemical degradation classification and important products of the following classes.
Unit:- 1
MEDICINAL CHEMISTRY – III
• Penicillin was discovered and introduced into therapy by Sir.
Alexander Fleming & Florey and Chain respectively
• Definition of Antibiotic
• Steps involved in commercial production of antibiotics
• Mechanism of action – overview
• Four methods of classification
History:
Modern Antibiotic era
• Initiated by the accidental discovery of the anti-bacterial
properties of Penicillin in 1929 by Sir Alexander Fleming
• Florey and Chain introduced Penicillin into therapy [1938]
• Definition (original) [By WAKSMAN (1942)]
• “ An antibiotic or antibiotic substance is a substance produced
by micro-organisms, which has the capacity of inhibiting the
growth and even of destroying other micro-organisms”
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Introduction Contd…
Modern Definition:
• “ Any substance produced by a living organism that is capable
of inhibiting the growth or survival of one or more species of
micro-organisms in low concentrations”
• Modified by Medicinal Chemists to include the substances
obtained from natural, semi-synthetic and synthetic sources
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Introduction Contd…
Hence a substance is classified as an antibiotic if the following
conditions are met:
• It is a product of metabolism
• It is a synthetic product produced as a structural analogue of a
naturally occurring antibiotic
• It antagonizes the growth or survival of one or more species of
micro-organisms
• It is effective in low-concentrations
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COMMERCIAL PRODUCTION: (of
antibiotics)
The general scheme of commercial production of antibiotics for
medicinal use may be divided into six steps:
• Preparation of a pure culture of the desired organism for
inoculation of the fermentation medium.
• Fermentation, during which the antibiotic is formed.
• Isolation of the antibiotic from the medium
• Purification
• Assays for potency, sterility, absence of pyrogens and other
necessary data
• Formulation into acceptable and stable dosage forms.
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MECHANISM OF ACTION
• Mechanisms of action of some common antibiotics are as follows:-
Site of action Antibiotic Process interrupted Type of
activity
1 Cell wall Penicillins Cell-wall cross linking Bactericidal
Cephalosprins Cell-wall cross linking Bactericidal
Cycloserine Bactericidal
Synthesis of Cell wall peptides
Vancomycin Muco-peptide synthesis Bactericidal
Bacitracin Muco-peptide synthesis Bactericidal
2 Cell membrane Amphotericin B Membrane function Fungicidal
Nystatin Membrane function Fungicidal
Polymyxins Membrane Integrity Bactericidal
3 Ribosomes Chloramphenicol Protein synthesis Bactericidal
50 S subunit Erythromycin Protein synthesis Bactericidal
Lincomycins Protein synthesis Bactericidal
30 S subunit Aminoglycosides Protein synthesis & fidelity Bactericidal
Tetracyclines Protein synthesis Bacteriostatic
4 Nucleic Acids Actinomycin DNA & mRNA synthesis Pancidal
Griseofulvin Cell division, microtubule Fungicidal
Assembly
DNA and /or Mitomycin DNA synthesis Pancidal
RNA Rifampin mRNA synthesis www.remixeducation.in
Bactericidal
MECHANISM OF ACTION Contd…
“ ANTIBIOTICS THAT INTERFERE WITH THE METABOLIC SYSTEMS
FOUND IN MICRO-ORGANISMS AND NOT IN MAMALIAN CELLS
ARE THE MOST SUCCESSFUL ANTI-INFECTIVE AGENTS”
For example,
• Antibiotics that interfere with the synthesis of bacterial cell walls
have a high potential for selective toxicity.
Cycloserine is an antimetabolite of D-Alanine, a constituent of
bacterial cell wall.
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MECHANISM OF ACTION Contd…
Many antibiotics like aminoglycosides, tetracyclines etc selectively
interfere with microbial protein synthesis or nucleic acid synthesis
like Rifampin.
Others like polymixins and polyenes, interfere with the integrity and
function of microbial cell membranes.
• The agents may be a bactericidal or a bacteriostatic.
• This distinction is important for the treatment of serious, life-
threatening infections, particularly if the natural defense
mechanisms of the host are either deficient or overwhelmed by the
infection – in such cases, a bactericidal is indicated.
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CLASSIFICATION (of Antibiotics)
• Various criteria are used to classify ‘ Antibiotics’
I method:
Based on the clinical effectiveness, spectrum of activity and degree
of selectivity.
Class 1:- Those inhibiting only one group of micro-organisms
• “Narrow Spectrum Antibiotics” eg. Nystatin and Bacitracin.
• Exhibit a high degree of selectivity.
Class 2:- Those inhibit both “Gram +Ve” and “Gram -Ve” bacterial and
/or other intracellular organisms.
• “ Broad Spectrum Antibiotics” eg. Chloramphenicol and Tetracyclin.
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CLASSIFICATION (of Antibiotics)
contd…
II method: based on the sources from which antibiotics are
obtained. They can be classified as
a. Natural:- obtained from the large scale fermentation of micro-
organisms.
Eg. ‘ Bacitracin’ and ‘Polymixin’ are obtained from some bacilli.
‘Streptomycin’ and ‘Tetracycline’ are obtained from streptomyces
species
b. Semi-synthetic:- The precursors of these antibiotics are obtained
from natural source. Synthetic method is utilized to produce the
analogues/derivatives of these precursors.
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CLASSIFICATION (of Antibiotics)
contd…
For example: 6-Aminopenicillanic acid is obtained from the cultures
of P. Chrysogenum. During the commercial production of benzyl
penicillin (Penicillin G), Phenyl acetic acid is added to the medium in
order to get the product.
c. Synthetic:- This class includes antibiotics which are having purely
synthetic origin.
• For example: Chloramphenicol (a broad spectrum antibiotic),
ciprofloxacin,etc
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CLASSIFICATION (of Antibiotics)
contd…
III method: based on the differences in the mechanism of action.
A. Drugs that interferes with the biosynthesis of bacterial cell-wall
Eg. Penicillins, Cephalosprins, Cycloserin, Bacitracin & Vancomycin.
B. Drugs that interfere in the functioning of Cytoplasmic membrane.
Eg. Polymixins, Aphotericin B and Nystatin.
C. Drugs that interfere with the protein biosynthesis.
Eg. Erythromycin, Lincomycins, Tetracyclines and Chloramphenicol.
D. Drugs that interfere with Nucleic acid biosynthesis
Eg. Actinomycin, Griseofulvin and Rifampin.
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CLASSIFICATION (of Antibiotics)
contd…
IV method: based on the chemical structure.
Β-lactam Antibiotics:
Eg. Penicillins, Cephalosprins, Monobactams.
Aminoglycosides:
Eg. Kanamycin, Streptomycin, Gentamycin, Neomycin, etc.
Tetracycline Antibiotics:
Eg. Tetracycline, Chlortetracycline, Oxytetracycline, etc.
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CLASSIFICATION (of Antibiotics)
contd…
Peptide Antibiotics:
Eg. Amphomycin, Tyrothricin, Bacitracin, etc.
Macrolide Antibiotics:
Eg. Erythromycin, Oleandomycin
Lincomycin:
Eg. Lincomycin, Clindamycin, pirlimycin
Unclassified Antibiotics:
Eg. Chloramphenicol, Rifamycin.
“Anti-fungal Antibiotics”
Eg. Griseofulvin, Polyene Antibiotics (Amphotericin B, Nystatin, Candicidin)
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Summary
• Penicillin was discovered and introduced into therapy by Sir.
Alexander Fleming & Florey and Chain respectively
• Definition of Antibiotic
• Steps involved in commercial production of antibiotics
• Mechanism of action - overview
• Four methods of classification
- Subject:- Medicinal chemistry 3
- Course:- B.pharm (pharmacy),
- Semester:- 6th sem , sem :- 6
