This document provides a summary of the history and properties of penicillin. It discusses how Alexander Fleming accidentally discovered penicillin in 1928 when he observed that a mold in one of his culture dishes was releasing a substance that killed surrounding bacteria. Later researchers were able to isolate and purify penicillin, which paved the way for its clinical use. The document also describes the structure of penicillin including its beta-lactam ring and how its mechanism of action involves binding to bacterial cell walls. Common uses and side effects of penicillin are also summarized.

1. STORY OF
PENICILLIN
By
Anupama Paul
Roll no. - 34
2nd Semester
Life science & bioinformatics
Assam University, Silchar

2. CONTENTS
 Introduction
 Historical background
 Structure
 Classification
 Mechanism of action
 Therapeutic uses
 Adverse effects
 Conclusion

3. INTRODUCTION
 An antibiotic is any chemical substances that are able
to kill microorganisms and cure infections.
 Greek words: anti = against ; bios = life
 The word antibiotic came from the word antibiosis,a
term coined in 1889 by Louis Pasteur's pupil Paul
Vuillemin which means a process by which life could
be used to destroy life.
 Penicillin are antibiotics produced by microorganisms
that kill other microorganisms

4.  Penicillin was the world’s first antibotic was discovered by
Sir Alexander Fleming in 1928 on accident.
 Alexander Fleming, noticed that one of his experimental
cultures of Staphylococcus was contaminated with mold,
which caused the bacteria to lyse . Since mold belonged
to the family Penicillium , he named the antibacterial
substance penicillin.
INTRODUCTION

5.  It was in 1928 when Sir Alexander Fleming, a scotish
biologist observed while experimenting on
Staphylococcus bacteria that a common fungus
inhibiting the growth of organism.
 It was an accident i.e. happening by chance, in his
laboratory in the basement of St. Mary's Hospital in
London.
 He defined new horizons for modern antibiotics with
his discoveries of enzyme lysozyme(1921) and the
antibiotic substance penicillin (1928). The discovery
of penicillin from the fungus Penicillium notatum
perfected the treatment of bacterial infections .
HISTORY OF PENICILLIN

6.  On Friday, September 28, in 1928, Fleming left the lid off of
one of his Petri dishes for several weeks, and a fungal spore
landed on it . After returning from vacation, Fleming noticed
that his Staphylococcus (bacteria) culture was contaminated
with this fungus which cause the bacteria to die . He then
carefully examined it first.
 He grew a pure culture and discovered that it was a Penicillium
mould, now known to be Penicillium notatum.
 He concluded that Penicillium mold must be secreting an
antibacterial substance, which he isolated first in crude form of
the active substance and named it as penicillin.
HISTORY OF PENICILLIN

7.  This newly discovered active substance(penicillin) was effective
even when diluted up to 800 times.
 Unfortunately, the substance was also unstable and Fleming
was unable to isolate and purify the compound. He therefore
came to the conclusion that penicillin was too unstable to be
used clinically.
 Florey and Chain in 1938 by using processes such as freeze-
drying and chromatography which allowed isolation of pure form
of penicillins .
 Fleming, Florey, and Chain shared the 1945 Nobel Prize for their
medicinal work on penicillin.
 The discovery and development of penicillin was a milestone in
20th century in the field of pharmaceutical chemistry.
HISTORY OF PENICILLIN

8. STRUCTURE OF PENICILLIN
 Penicillins are called beta – lactam antibiotics and are
characterized by three fundamental structural requirements:
A) Beta-lactam ring
B) Thiazolidine ring and
C) Side chains
 A beta-lactam (β-lactam) ring is a four-membered (A lactam is a
cyclic amide.) It is named as such because the nitrogen atom is
attached to the β-carbon atom relative to the carbonyl group.
 Thiazolidine is a heterocyclic organic compound with the formula
(CH2)3(NH)S. It is a 5-membered saturated ring with a thioether
group and an amine group in the 1 and 3 positions respectively.
 The side chains determines in large part, the antibacterial
spectrum and the pharmacologic properties.

9. STRUCTURE OF PENICILLIN
FIG: Chemical structure of Thiazolidine
ring
Fig: A simplest β-lactam ring

10.  In a complete structure of penicillin,the beta lactam ring
and thiazolidine ring fused together are necessary for
antibacterial activity and the side chains determines the
antibacterial spectrum and pharmacologic properties.
 The carboxylic acid side chain PBP (Penicillin Binding
Protein) recognition and the R group on acylamino side
chain changes with different beta lactam antibiotics and
effects the characteristics of the molecule which results
in formation of different types of penicillin.
STRUCTURE OF PENICILLIN

11. STRUCTURE OF PENICILLIN
Fig: Penicillin core structure, where "R" is the
variable group

12. CLASSIFICATION OF PENICILLIN
 The penicillins can be classified according to their
antibacterial activity:
1)Natural penicillins
2)Synthetic penicillin
-Antistaphylococcal penicillins
-Aminopenicillins
-Extended spectrum penicillins
 Natural penicillins, the first agents in the penicillin
family, are obtained directly from the Penicillium mold
and do not require further modification.eg: Penicillin G

13.  The antistaphylococcal penicillins (also called the "penicillinase-
resistant penicillins") have bulky side chains that prevent their
inactivation by the staphylococcal β-lactamases. These penicillins
are useful in treating infections caused by Staphylococcus aureus
and Staphylococcus epidermidis. eg:Cloxacillin, Nafcillin
 The aminopenicillins have a wider range of activity than natural or
antistaphylococcal penicillins. However, they lack the bulky side
groups and are susceptible to inactivation by beta-lactamases.eg:
eg:Cyclacillin, Ampicillin
 Extended spectrum penicillins are similar to the aminopenicillins in
structure but have either a carboxyl group or urea group instead of
the amine eg:Crboxypenicillin, Ureidopenicillin.
CLASSIFICATION OF PENICILLIN

14. MECHANISM OF ACTION
Fig: Penicillin blocking the construction of bacterial cell wall by binding with PBP
and thus weakening and causing break of cell wall , finally killing the bacteria.

15. MECHANISM OF ACTION
1) The bacterial cell wall consists of
strands of repeating NAG and NAM . The
NAM subunits have short peptide chain
attached to them The proximal alanine is
usually L-ala and distal two are D-ala.
2)The PBP binds the peptide side chains
and forms cross link with the expulsion of
one D-alanine from one peptide side chain
3)The PBP dissociates from the cell wall
once the cross link is formed
4)Penicillin is added to the system. It
enters the active site of the PBP and reacts
with the serine group that is important in
its enzymatic activity
5)The beta lactam ring of penicllin is
irreversible opened during the action of
PBP and remain parmanently linked to the
PBP thus blocking its active site.

16.  Penicillin is used to treat different types of infections caused by
bacteria , such as-
 Ear and lung infections.
 Streptococcal infction
 Urinary tract infections.
 Respiratory tract infection
 It may used to skin and soft tissue infections.
 Intra abdominal infection
 Syphilis, gonorrhea
 Diptheria etc.
THERAPEUTIC USES

17. ADVERSE EFFECTS
 Diarrhea that is watery or bloody;
 Fever, chills, body aches, flu symptoms;
 Easy bruising or bleeding, unusual weakness;
 Urinating less than usual or not at all;
 Severe skin rash, itching, or peeling;
 Agitation, confusion, unusual thoughts or behavior; or
 Seizure (black-out or convulsions).
 Nausea, vomiting, stomach pain;
 Vaginal itching or discharge;
 Swollen, black, or "hairy" tongue
 Diarrhea
 Vomiting , Nausea and Stomach pain.
 Headache
 Thrush( white patches inside mouth or throat)

18.  It has excellent tissue penetration
 It is bactericidal against sensitive strain
 It is inexpensive
 Modified penicillins are resistant to stomach
acid and has broader spectrum
 It is efficacious in treatment of infections
ADVANTAGES

19. DISADVANTAGES
 Most of thhe penicillins are destroyed by the
gastric acid
 Penicillin lack activity against gram negative
organisms
 It shows drug hypersensitivity
 It has short duration of action and given in
short intervals

20. CONCLUSION
Penicillin has impacted the world so much. If it had not been
discovered , most of the people living now would be dead from
infection .When Fleming discovered penicillin , he at first
thought it was useless. But thanks to Ernst Chain and Howard
Florey , his discovery was not left behind forever . This drug has
helped our economy , government and social life in many ways
for the better.

21. THANK YOU

22. REFERENCES
 Tortora Gerard.J. Funke B.R. Case C.L. “Microbiology- An
introduction.” pg:230-242
 http://www.emedexpert.com/compare/penicillins.shtml
 https://www.slideshare.net/banuman35/penicillins-by-dr-
panchumarthy-ravisankar-mpharm-phd?qid=2e90959e-4ea0-
4961-9d5d-5e77cdc9ca82&v=&b=&from_search=2
 https://www.pbs.org/newshour/health/the-real-story-behind-
the-worlds-first-antibiotic
 https://commons.wikimedia.org/wiki/File:Penicillin_inhibition.s
vg
 https://www.drugs.com/penicillin.html