5. INTRODUCTION
Penicillin is a group
of antibiotics that are
used in the treatment
of various bacterial
infections.
Penicillin is derived
from the Penicillium
mould.
6. • 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.
7. HISTORY
Penicillin, the world's first antibiotic, was
discovered by British scientist Alexander
Fleming in 1928 on accident.
8. 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.
9. 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.
10. Structure
Penicillins as well as cephalosporins are
called beta-lactam antibiotics and are
characterized by three fundamental
structural requirements:
11.
12. 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
13. Mechanism of action
Penicillins 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.
15. The compound consists of 2 basic
structures:
1. Thiazolidine Ring
2. Beta-Lactam Ring
H
R H
N
S
CH3
2 1
O
N CH3
O
COOH
16. - site of attachment of side chain, R,
which determines many of the
antibacterial and pharmacologic
characteristics of a derivative
(Spectrum and penicillin-resistance)
17. 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.
18.
19. Thiazolidine ring (A) connected to a b-lactam ring
(B), to which is attached a side chain (R).
20. 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
24. SAR of Penicillins
O
H H
S
N
H
N
O
H COOH
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.
25. O
H H
S
N
H
N
O
H COOH
Three chiral centers are
requirement for Penicillins
bioactivity
26. Side chain can be replaced with different
R group to obtain different compounds
With broad antibacterial spectrum
O
H H
S
N
H
N
O
H COOH
27. Structural Activity Relationship
Position 1 – When the
H 1
sulfur atom of R N
H
5
S
2
CH3
6
the thiazolidine ring is B A CH3
O 3
N
oxidized to a sulfone or 7 4
O COOH
sulfoxide, it improves
acid stability, but
decreases the activity of
the agent.
28. Position 2 – No substitutions allow at
this position, any change will lower
activity. The methyl groups are
necessary
H 1
H S CH3
R N
6 5 2
A CH3
B
O 3
N
7 4
O COOH
29. Position 3 – The carboxylic acid of
the thiazolidine is required for activity. If it
is changed to an alcohol or ester, activity
is decreased.
H 1
H S CH3
R N
6 5 2
A CH3
B
O 3
N
7 4
O COOH
30. Position 4 – The nitrogen is a must.
Position 5 – No substitutions allowed.
H 1
H S CH3
R N
6 5 2
A CH3
B
O 3
N
7 4
O COOH
31. Position 7 – The carbonyl on the Beta-
lactam ring is a must.
H 1
H S CH3
R N
6 5 2
A CH3
B
O 3
N
7 4
O COOH
32. •
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.
• H 1
H S CH3
R N
6 5 2
A CH3
B
O 3
N
7 4
O COOH
33. 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.
H 1
H S CH3
R N
6 5 2
A CH3
B
O 3
N
7 4
O COOH
34. 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;
35. severe skin rash, itching, or peeling;
agitation, confusion, unusual thoughts
or behavior;
seizure (black-out or convulsions).
nausea, vomiting, stomach pain;
36. vaginal itching or discharge;
headache;
swollen, black, or "hairy" tongue; or
thrush (white patches or inside your
mouth or throat).
