4. INTRODUCTION
• Penicillin is derived from the Penicillium mould.
•It destroys bacteria by inhibiting the enzymes responsible for the formation
of the cell wall in the bacterial cells.
Penicillin is a group of antibiotics that are commonly used to treat different
types of gram positive and gram negative bacterial infections. In their
structure, beta-lactam ring is located due to this reason these drugs are also
called as beta-lactam antibiotics.
5. HISTORY
Penicillin, the world's first antibiotic, was discovered by British
scientist Alexander Fleming in 1928 on accident.
In 1928 Alexander Fleming discovered the compound
produced by the fungus.
The fungus was called Penicillium notatum.
The isolated compound he called Penicillin.
Fleming noted a fungus growing on his bacterial
plates had killed off the surrounding bacteria.
Fleming, Florey and Chain received a Nobel prize
in 1945 for medicine for their work on penicillin.
6. Fleming accidentally left a dish of staphylococcus bacteria uncovered for a few
days. He returned to find the dish dotted with bacterial growth, apart from one
area where a patch of mold (Penicillin notatum) was growing.
This newly discovered active substance penicillin
was effective even when diluted up to 800 times.
7.
8. Penicillins as well as cephalosporins are called beta-lactam antibiotics
and are characterized by three fundamental structural requirements:
The fused beta-lactam & Thiazolidine ring structure.
A free carboxyl acid group.
One or more substituted amino acid side chains.
STRUCTURE
CHEMISTRY OF PENICILLINS
9. Result: bacteria cells die from cell lysis.
Penicillins do not kill other cells in the
body.
MECHANISM OF ACTION
Penicillins are bactericidal antibiotics as they kill the microorganisms
when used at therapeutic dose.
The synthesis of cell wall of bacteria is completely depended upon an
enzyme named as transpeptidase.
Primarily, Penicillin inhibits the cell wall of bacteria by blocking transpeptidase
after binding to penicillin-binding protein (PBP) and prevents its synthesis.
10. N
S
NH
COOH
O
COR
1
2
34
56
7
Nomenclature of penicillins is done to different systems:
Chemical abstract system(CAS):
According to this system penicillins are numbered starting from “S” atom.
Sulfur atom is assigned the 1st position and “N” atom is assigned number 4th
position and is called 6-acylamino-2,2-dimethyl-3-corboxylic acid.
Nomenclature
United states Pharmacopoeia (USP system):
The USP system of naming penicillins is the reverse of CA system.
According to this system the nitrogen atom is given the 1st position and “S”
atom is assigned the 4th position and is called 4-thia-1-azabicyclo heptone.
11. N
S
O
H
NC
O
R
Penicillin
CH3
CH3
COOH
N
S
Penillic acid
CH3
CH3
COOH
H
C
N
HOOC
C
R
Dilute acid
H / HgCl2
HN
S
COOH
H
NC
O
R
Penicilloic acid
CH3
CH3
COOH
HN
S
COOCH3
H
NC
O
R
Penicilloic acid
CH3
CH3
COOH
HN
S
H
NC
O
R
Penilloic acid
CH3
CH3
COOH
H2
C
CHO
H2N
HS
H
C
COOCH3
H
NC
O
R
Methylpenaldate
CH3
CH3
COOH
Penicillamine
Acidic PH
A
lkaline
PH
N
aO
H
lactam
ase
/Pencillinase
CH3
O
H
Decarboxylation
HgCl2
N
S
O
H2N
6-APA
CH3
CH3
COOH
Am
idase
Penilloaldehyde Penicillamine
CHEMICAL
DEGRADATION OF
PENICILLINS
14. Position 1 – When the sulfur atom of the Thiazolidine ring is oxidized to
a sulfone or sulfoxide, it improves acid stability, but decreases the activity of
the agent.
Position 2 – No substitutions allow at this position, any change will lower
activity. The methyl groups are necessary
Position 3 – The carboxylic acid of the Thiazolidine is required for activity. If
it is changed to an alcohol or ester, activity is decreased.
Position 4 – The nitrogen is a must.
Position 5 – No substitutions allowed.
Structural Activity Relationship (SAR)
N
S CH3
CH3
O
H
COOH
N
O
R
H
B A
1
2
3
5
4
6
7
15. Position 7 – The carbonyl on the Beta-lactam ring is a must.
Position 6 – Substitutions are allowed on the side chain of the amide.
An electron withdrawing group added at this position will give the
compound better acid stability because this substitution will make the
amide oxygen less nucleophillic.
A bulky group added close to the ring will make the compound more
resistant to Beta-lactamases.
Steric hindrance provides protect to the Beta-lactam ring.
16. N
S
HH
O
COOH
N
H
H
O
The presence of a carboxy group is a requirement for PBP
recognition. When esterition of it, it behaves a pro-drug the
bioavailability will be raisen.
Side chain can be replaced with different R group to obtain
different compounds with broad antibacterial spectrum.
Three chiral centers are requirement
for Penicillins Bioactivity.
18. ADVERSE EFFECTS
Diarrhea that is watery or bloody.
Fever, chills, body aches, flu symptoms.
Urinating less than usual or not at all.
Severe skin rash, itching, or peeling.
Agitation, confusion, unusual thoughts or
behavior.
Seizure (black-out or convulsions).
Nausea, vomiting, stomach pain.
Vaginal itching or discharge.
Headache.
Thrush (white patches or inside your mouth or
throat).