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Seminar onpenicillin's
Seminar onpenicillin's
By R.Ganesh
08Z41R0046IV/IV B.PHARMACY
Under the guidance
of
T. Kala Praveen sir, M.pharm.
Dept.of Pharm.chemistry.
INKOLLU-523167(Affiliated to J.N.T.University , Approved by
AICTE)
D.C.R.M PHARMACY COLLEGE
CONTENTSCONTENTS
INTRODUCTION
HISTORY
MECHANISM OF ACTION
CHEMISTRY
CLASSIFICATION
STRUCTURAL ACTIVITY RELATIONSHIP
ADVERSE EFFECTS
USES
INTRODUCTION
Penicillin is a group
of antibiotics that
are used in the
treatment of
various bacterial
infections.
Penicillin is derived
from the
Penicillium mould.
• It can be used to treat ailments such as strep throat, spinal meningitis, gangrene, and syphilis.
• It destroys bacteria by inhibiting the enzymes responsible for the formation of the cell wall in the bacterial cells.
HISTORYPenicillin, the world's first antibiotic,
was discovered by British scientist Alexander Fleming in 1928 on accident.
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.
The mold produced a substance,
named penicillin by Fleming.
Penicillin was finally isolated by
Howard Florey and Ernst Chain.
Fleming, Florey and Chain
received a Nobel prize in 1945.
Structure
Penicillins as well as cephalosporins
are called beta-lactam antibiotics and
are characterized by three
fundamental structural requirements:
the fused beta-lactam structure
a free carboxyl acid group
one or more substituted amino acid
side chains
The Beta-lactam structure can also
be viewed as the covalent bonding
of pieces of two amino acids -
cysteine and valine
Mechanism of actionPenicillins enter the bacteria via the
cell wall.
Inside the cell, they bind to penicillin-binding protein.
Once bound, normal cell wall synthesis is disrupted.
Result: bacteria cells die from cell lysis.
Penicillins do not kill other cells in the body.
Chemical Properties of Penicillins
The compound consists of 2
basic structures:
1. Thiazolidine Ring
2. Beta-Lactam Ring
N
NS
O
O
H
CH3
CH3
COOH
H
R
12
- site of attachment of side
chain, R, which determines
many of the antibacterial and
pharmacologic characteristics
of a derivative (Spectrum and
penicillin-resistance)
Derivatives of benzylpenicillin,
from which the methyl benzene
radical is split off by amidase
producing
6-aminopenicillanic acid, the
parent compound of
All semisynthetic penicillins.
Thiazolidine ring (A) connected to a b-lactam ring (B), to which is attached a side chain (R).
The penicillin nucleus itself is the
chief structural requirement for
biological activity;
metabolic transformation or chemical
alteration of this portion of the
molecule causes loss of all significant
antibacterial activity
CLASSIFICATION
Natural penicillins
Penicillinase-resistant penicillins
Aminopenicillins
Extended-spectrum penicillins
Natural penicillins
penicillin G, penicillin V potassium
Penicillinase-resistant penicillins
cloxacillin, dicloxacillin, methicillin,
nafcillin, oxacillin
Aminopenicillins
• amoxicillin, ampicillin, bacampicillin
Extended-spectrum penicillins
• piperacillin, ticarcillin, carbenicillin,
mezlocillin
SAR of Penicillins
N
SHH
OCOOH
NH
H
O
The presence of a carboxy group is a requirement for PBP recognition.
When esterition of it, it behaves a pro-drugThe bioavailability will be raisen.
N
SHH
OCOOH
NH
H
O
Three chiral centers are requirement for Penicillins
bioactivity
N
SHH
OCOOH
NH
H
O
Side chain can be replaced with differentR group to obtain different compounds
With broad antibacterial spectrum
Structural Activity Relationship
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.
•
N
S CH3
CH3
O
H
COOH
N
O
R
H
B A
1
2
3
5
4
6
7
Position 2 – No substitutions allow
at this position, any change will
lower activity. The methyl groups
are necessary
N
S CH3
CH3
O
H
COOH
N
O
R
H
B A
1
2
3
5
4
6
7
Position 3 – The carboxylic acid of
the thiazolidine is required for
activity. If it is changed to an alcohol
or ester, activity is decreased.
N
S CH3
CH3
O
H
COOH
N
O
R
H
B A
1
2
3
5
4
6
7
Position 4 – The nitrogen is a must.
Position 5 – No substitutions allowed.
N
S CH3
CH3
O
H
COOH
N
O
R
H
B A
1
2
3
5
4
6
7
Position 7 – The carbonyl on the Beta-
lactam ring is a must.
N
S CH3
CH3
O
H
COOH
N
O
R
H
B A
1
2
3
5
4
6
7
•
Postion 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.•
N
S CH3
CH3
O
H
COOH
N
O
R
H
B A
1
2
3
5
4
6
7
A bulky group added close to the
ring will make the compound more
resistant to Beta-lactamases.
Steric hinderence provides protect
to the Beta-lactam ring.
N
S CH3
CH3
O
H
COOH
N
O
R
H
B A
1
2
3
5
4
6
7
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;
seizure (black-out or convulsions).
nausea, vomiting, stomach pain;
vaginal itching or discharge;
headache;
swollen, black, or "hairy" tongue; or
thrush (white patches or inside
your mouth or throat).
Therapeutic Uses
• Pneumococcal Infections
– Pneumococcal Meningitis
– Pneumococcal Pneumonia
• Streptococcal Infections
– Streptococcal Pharyngitis
(including Scarlet Fever)
- Streptococcal Pneumonia,
Arthritis,
Meningitis, and Endocarditis
• Staphylococcal Infections
• Meningococcal Infections
• Gonococcal Infections
• Syphilis
• Actinomycosis
• Diphtheria
• Anthrax
• Clostridia Infections
• Surgical Procedures in Patients with
Valvular Heart Disease.