Pharmacology and development of
Antibiotics (Penicillin) and
Antiseptics
13/02/13
By:
Mohit Kumar Sharma
PhD Final year
Cell types
Eukaryotic cell
Prokaryotic cell
Bacterial classification based on
Gram staining
Gram staining technique
Bacterial classification based on Gram staining
Gram positive
Gram negative
Peptidoglycan
Transpeptidase cross-linking to peptidoglycan sheets
Few Examples of different classes of Bacteria
Protection against bacteria
- Skin
- Tears
- Saliva
- Stomach acid
Skin
The skin is tough, dry, salty, oily, rich in fatty acids and urea, low in
nutrients (lots of dead, empty cells) & thick. The sweat glands secrete a
mixture of salt & fatty acids that inhibit many microbes.
Tears
Lysozyme is an enzyme, present in tears that LYSES many prokaryotic
cells by digesting the peptidoglycan in their cell walls.
- Through hydrolysis of glycosidic linkages.
Saliva
There is a continuous flow of fluid (saliva) through the mouth which
FLUSHES loose microbes into the stomach.
Stomach acid
The stomach contains a strong (hydrochloric) acid. Many microbes are
killed by this acidic environment and digested by the proteolytic enzymes
in the digestive system.
What are Antibiotics?
- Antibiotics, also known as antibacterials, are types of medications that
destroy or slow down the growth of bacteria.
- The term antibiotic was first used in 1942 by Selman Waksman
- The Greek word anti means "against", and bios means "life" (bacteria are life
forms).
- Many antibacterial compounds are relatively small molecules with a
molecular weight of less than 2000 atomic mass units
- The first antibiotic was penicillin.
- Penicillin-related antibiotics such as ampicillin, amoxicillin
benzylpenicilllin are widely used today to treat a variety of infections.
and
How do antibiotics work?
Although there are a number of different types of antibiotic they
all work in one of two ways:
- A bactericidal antibiotic kills the bacteria. Penicillin is a
bactericidal. A bactericidal usually either interferes with the
formation of the bacterium's cell wall or its cell contents.
- A bacteriostatic stops bacteria from multiplying.
Targets of Antimicrobials
4. Protein synthes is inhibitors acting
on ribosomes
1. Cell wall inhibitors
Block synthesis and repair
Penicillins
Cephalosporins
Carbapenems
Vancomycin
Bacitracin
Fosfomycin
Isoniazid
Ribosome
Erythromycin
Clindamycin
Synercid
Pleuromutilins
Substrate
2. Cell membrane
Causelossofselective permeability
Polymyxins
Daptomycin
Enzyme
Product
Site of action
30S subunit
Aminoglycosides
Gentamicin
Streptomycin
Tetracyclines
Glycylcyclines
Both 30S
and 50S
3. DNA/RNA
Inhibit replication and transcription
Inhibit gyrase(unwinding enzyme)
Quinolones
Inhibit RNA polymerase
Rifampin
Site of action
50S subunit
Blocks initiation of protein
synthesis
Linezolid
mRNA
DNA
5. Folic acid synthesis
Block pathways and inhibit
metabolism
Sulfonamides (sulfa drugs)
Trimethoprim
Mechanisms of Drug Action
 Inhibition of cell wall synthesis
 Inhibition of nucleic acid structure and function
 Inhibition of protein synthesis
 Interference with cell membrane structure or function
 Inhibition of folic acid synthesis
Penicillin
History of Penicillin
- 1928, Alexander Fleming - Observed antibiosis against
bacteria by a fungus of the genus Penicillium.
- 1940, Florey and Chain - Began work on isolating and
synthezing large amounts of Penicillin.
- 1940, Preclinical trials in mice
- 1941, Phase II Clinical trial
- 1944 - Used in WWII to treat infections
- Late 1940’s - available for general use in US
Alexander Fleming
Antibiotic effect of the mold Penicillium chrysogenum
Staphylococcus
aureus
(bacterium)
Penicillium
chrysogenum
(fungus)
Zone where
bacterial growth
is inhibited
Penicillin
 Source: Penicillin chrysogenum
 Penicillin antibiotics grouped into generations
based on spectrum of anti-microbial activity. (1st,
2nd , 3rd and 4th generations)
 Natural (penicillin G and V)
 Semisynthetic (Ampicillin, Carbenicillin)
Classification

Penicillins (penicillin G) – greatest activity against gram+,
gram-cocci, non-beta-lactamase-producing anaerobes

Antistaphylococcal penicillins (nafcillin) – resistant to
staphylococcal beta-lactamases, active to staphylococci and
streptococci

Extended-spectrum penicillins (ampicillin) – retain
antibacterial spectrum of penicillin with improved activity
against gram- organisms, but are destroyed by beta-lactamases.
Types of Penicillin
Chemical Structure
Penicillins as well as cephalosporins are called beta-lactam
antibiotics, characterized by 3 fundamental structural
requirements:



the fused beta-lactam structure
a free carboxyl acid group
one or more substituted amino acid side chains
Chemical structure of penicillins
Structure
Thiazolidine ring
Beta-lactam ring
Variable side chain
(R group)
- The R group is responsible for the
activity of the drug and can be
changed to improve activity of the
antibiotic.
- Cleavage of the beta-lactam ring
will render the drug inactive.