Story of penicillin

describes the discovery, structure, types, mode of actionand various uses of pencillin

1. Story of Penicillin By Anupama Paul Roll no. - 34 2 nd 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 20 th 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.svg https://www.drugs.com/penicillin.html