1. Branch – PHARMACY
Medicinal Chemistry III (BP 601T)
DR. APJ ABDUL KALAM TECHNICAL UNIVERSITY
By
Dr. Rakhi Mishra
Associate Professor
NIET (Pharmacy Institute)
Greater Noida
Lecture – 4
Beta Lactam Antibiotics- (Part-4)
2. β-lactamase Inhibitors
• β-lactamases are a family of enzymes produced by
many gram-positive and gram negative bacteria that
inactivate β-lactam antibiotics by opening the β- lactam
ring.
•Has negligible antibacterial activity or very weak
antibacterial action.
•Important in combination with penicillins sensitive to
β-lactamase degradation.
•Given with Penicillins which increases spectrum of
activity .
•Microbial resistance to beta lactam antibiotics.
4. β-lactamase Inhibitors
CLAVULANIC ACID
•Clavulanic acid is the first one of this class.
•It is natural product from streptomyces.
•Has a rapid oral absorption
•Addition of clavulanicacid re-establishes the activity of
amoxicillin
• Indicated for Respiratory tract, Skin & Soft tissue,
intra abdominal infections.
• Dosage : 100mg/kg/day in 4 divided doses
5. β-lactamase Inhibitors
SULBACTAM
• 2–3 times less potent than clavulanic acid
• Oral absorption of sulbactam is inconsistent,
therefore preferably given parentrally.
• It has been combined with ampicillin for use against
the β-lactamase
• Used commonly in surgical infections and gonorrhea.
• Dosage:- Ampicillin with Sulbactum:
200mg/kg/day in 4 divided doses.
6. β-lactamase Inhibitors
TAZOBACTUM
•It is similar to sulbactam.
•Its pharmacokinetics matches with piperacillin with
which it has been combined for use in severe infections
like peritonitis, pelvic/urinary/respiratory infections
caused by β-lactamase producing bacilli.
•Dosage:-Piperacillin+Tazobactum: 200-300mg/kg/day
in 3 divided doses
7. β-lactamase Inhibitors
MECHANISM OF ACTION
• β-lactamases are a family of enzymes produced by
many gram-positive and gram-negative bacteria that
inactivate β-lactam antibiotics by opening the β-lactam
ring.
• β-lactamases (β-lactamases, also known as
Penicillinase) that provide multiresistance to β-lactam
antibiotics.
•Beta lactam inhibitors binds to β-lactamase enzyme and
inactivate them
8. β-lactamase Inhibitors
β-lactam Antibiotic β-lactam Antibiotic + β-lactamase inhibitors
Contains β-lactam ring Complex
Inactive compounds Effectiveness of β-lactamase is diminished
Enhances the activity of β-lactam antibiotic
10. β-lactamase Inhibitors
STRUCTURE ACTIVITY RELATIONSHIP
• β-Lactam Ring is essential
• Sulphur of penicillin is replaced by O
• No substitution at C-6 is required fro the activity
• Carboxylic acid is essential for the activity.
• R stereochemistry is good at C-3
12. MONOBACTAMS
• Monobactams are β-lactam compounds wherein the β-
lactam ring is alone and not fused to another ring, in
contrast to most other β-lactams.
•They are effective only against aerobic Gram-negative
bacteria. • (e.g., Neisseria, Pseudomonas).
• Other examples of monobactams are •aztreonam.
tigemonam, nocardicin A, •and tabtoxin.
•Aztreonam. (The four-membered ring at the bottom is
the β-lactam. There is a second thiazole ring, but it is not
fused to the β-lactam ring.)
13. MONOBACTAMS
AZTREONAM
•This drug is monocyclic β-lactam (monobactam)
•The four-membered ring at the bottom is the β-lactam.
•There is a second thiazole ring, but it is not fused to
the β-lactam ring.
14. MONOBACTAMS
•Aztreonam have highly polar structure which reduces
the oral bioavailability
•It is recommended to give parenterally
• The antimicrobial spectrum of aztreonam is different
from other beta lactams. It has resemblance to
aminoglycosides
• Limited activity against gram positive bacteria and
anaerobic bacteria.
15. MONOBACTAMS
MECHANISM OF ACTION
• Monobactams inhibit the bacterial growth by
interfering with the transpeptidase catalyze reaction of
bacterial cell wall synthesis
•Covalently binds to penicillin binding protein (PBP) to
prevent the growth of cell.
16. MONOBACTAMS
STRUCTURE ACTIVITY RELATIONSHIP
• Carboxyl group increases the
activity against Pseudomonas
•Amino thiazole group imparts
action against gram negative
bacterias
•4 alpha methyl group decreases its
degradation by beta-lactamase enzyme.
•Sulphonyl moeity increases the activity of beta lactam
ring
