1. PRESENTATION ON
SAR OF PENICILLIN & CEP
HALOSPORIN
Presented by -- RANJANA
GVM COLLEGE OF PHARMACY

2. SAR OF PENICILLIN
There are 2 rings in Penicillin structure:-
1. Thiazolidine ring
2. Beta - lactam ring

3. ◆Substitution on thiazolidine ring
• When the surface atom of thiazolidine
ring is oxidised to a sulfone(SO2) or sul
foxide (SO)
• It improves acid stability & decrease th
e antibacterial activity of the agent.
• Therefore sulphur atom is placed at po
sition 1 to retain desired activity.
• No substitution are allowe
d at this position
• Any change will lower the
antibacterial activity.
• Methyl group are necessar
y at this position.
PENICILLIN
1. SUBSTITUTION ON POSITION 1
2 . SUBSTITUTION AT POSITION 2
3 . SUBSTITUTION ON POSITION 3
• Carboxylic acid is required for antib
acterial activity, if it's change to alc
ohol or ester, activity will decrease.

4. SUBSTITUTION ON THIAZOLIDINE RING
4 . SUBSTITUTION ON POSITION 4
5 . SUBSTITUTION ON POSITION 5
• Nitrogen is required without any
substitution for antibacterial activ
ity.
• Position 5 must be unsubstituted bec
ause hydrogen of C-5 is required to
maintain chirality & Cis-formation of
the compound for antibacterial activ
ity.

5. SUBSTITUTION ON A BETA LACTAM RING
1. SUBSTITUTION ON POSITION 6
• It can be explained using Penicil
lin-G (Benzyl Penicillin).
• Stability of Benzyl Penicillin can
further be increased by substit
ution using an electron withdra
wing group (NH2, Cl, F, Br).
• Alpha substituted Benzyl Penici
llin is more stable then Benzyl P
enicillin Towards acid catalysed
hydrolysis.

6. SUBSTITUTION ON BETA LACTAM RING
• Increasing steric hindrance at alpha carbon,
increase Protection against-Lactamase resis
tance. Thus increases the antibacterial activ
ity.
• Steric hindrance, slow the reaction because
of presence of bulky groups.
• Thus increased stearic hindrance will increa
se antibacterial activity, as it will protect m
ore against beta-lactamase resistance.
• Carbonyl on beta - lactam ring
is must.
SUBSTITUTION ON POSITION 7
• Increased steric hindrance by thi
s substitution & also protect drug
from lactamase resistance.
• Eg:- 1.Methacillin (Ortho substitu
tion)2.Nafcillin (meta substitutio
n)
SUBSTITUTION ON ORTHO OR META
POSITION OF BENZYL RING
Continue (SUBSTITUTION ON
POSITION 6)

7. SAR OF CEPHALOSPORIN
There are 2 ring in CEPHALOSPORIN:-
1. Beta lactam ring
2. Dihydrothiazine ring

8. • Acylation of amino group increases the potency against gram-positive
bacteria, but it decreases gram-negative potency.
• High antibacterial activity is observed only when new acyl groups are d
erived from carboxylic acids for gram-positive bacteria.
• Substituents on aromatic ring that increases lipophilicity provide highe
r gram-positive activity and lower gram-negative activity.
• Phenyl ring in side-chain can be replaced with other heterocycles (like-
minded thiophene, furan, pyrimidine etc.) Which shows improved spec
trum of activity & Pharmacokinetic properties.
1. SUBSTITUTION ON 7- ACYLAMINO

9. 2. SUBSTITUTION ON C-3
• Nature of C-3 substituents influences pharmaco
kinetic & pharmacological properties as well as
antibacterial activity
• Modification at C-3 position has been made to r
educe the degradation of cephalosporin.
3.
3. DISPLACEMENT OF ACETOXY GROUP BY AZIDE ION YIELD DERIVA
TIVES WHICH RELATIVELY LOW GRAM-NEGATIVE ACTIVITY.

10. Displacement of 3-a
cetoxy group with a
romatic thiols will e
nhance the activity
against gram-negati
ve bacteria with imp
roved pharmacokin
etic properties.
• Replacement of ACET
OXY group at position
C-3 with -CH3, Cl has r
esulted in orally activ
e compounds.
• Carboxyl group of pos
ition-4 has been conv
erted into ester prodr
ugs to increase bioava
ilability of cephalospo
rin & these can be giv
en orally.
• Oxidation of ring sulph
ur to sulphoxide or sulp
hone greatly destroy th
e antibacterial activity.
• Replacement of sulphur
with oxygen leads to ox
acepham with increase
d antibacterial activity.
• Replacement of sulphur
with methylene group
has greater chemical st
ability & a longer half -
life.
3 4 5

11. That's all