SULBACTAM -BETALACTAMASE INHIBITOR,INTRODUCTION,MECHANISM OF ACTION,SAR,SYNTHESIS, USES. RAVISANKAR.p VIGNAN PHARMACY COLLEGE,VADLAMUDI,GUNTUR.

1. SULBACTUM
Prof.P.Ravisankar
Vignan Pharmacy college
Valdlamudi
Guntur Dist.
Andhra Pradesh
India

2. Beta Lactamase inhibitor sulbactum is beta lactum structure that have
Negligible antibacterial activity but inhibit beta lactamases.
Sulbactum can be administered alongside penicillins to protect them from
Beta lactamases and to broaden their spectrum of activity.
Betalactamase inhibitors are
Clavulanic acid
Tazobactum

7. *Sulbactam sodium is a derivative of the basic penicillin nucleus.
Sulbactam is a sulfone of penicillanic acid, is synthesized from 6-APA .
Both compounds have extremely weak antibacterial properties and act by forming
irreversible complexes with beta-lactamase, which inactivates the enzyme, and as a
result the beta-lactam antibiotic has time to destroy the microorganism.
*Sulbactam is a molecule that is given in combination with beta-
lactam antibiotics to inhibit beta-lactamase, an enzyme produced by
bacteria that destroys the antibiotics.
*Chemically, sulbactam sodium is sodium penicillinate sulfone;
sodium (2S, 5R)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate
4,4-dioxide.
*Its chemical formula is C8H10NNaO5S
*molecular weight of 255.22.
*The structural formula of
sulbactum is:
Chemistry of sulbactum:

8. No acylamino side chain at
6th position
Beta lactum ring
Free corboxylate essentialBicyclic system
Is important
Sulbactum mechanism is based on irreversible inhibitor and could be classed as a
Suicide substrate.
The drug fits the active site of betalactamase, and the beta lactum ring is opened by
Serine residue . The acyl-enzyme intermediate then reacts further with another enzymatic
Nucleophilic group(possibly NH2 ) to bind the drug irreversibly to the enzyme.
Sulfone group is essential and also
Enhances the activity.
The corbonyl on the
Betalactum at position -7 is must
N at position 1
Is must for activity.
Methyl groups at
Position 3 are required
For activty.
SAR (structure activity relationship )of Sulbactum

9. Structure activity relation ship (SAR)of Sulbactum:
1. Beta lactum ring(tetracyclic amide) is essential for the activity.
2.Any modifications result in an inactive compound.
3.Oxidation of sulphur to sulfone enchaces the activity.
4.Removal of oxygen atom from 4th position may result an inactive compound.
5.In sulbactum removal or substitution of hetero N atom by any other hetero atom
results in an inactive compound.
6.Removal of ketone bonds results in a new compound with reduced activity
or devoied of any activity.
7.Sulbactum should irreversibly bind with enzyme and inactivate it.
Rate and extent of formation of inhibitor-enzyme complex determines the potency.
-

11. Sulbactum synthesis

13. Most beta lactamases and as such is now used in combination with traditional
Pencillins such as amoxicillin(+ Clavulanic acid Augmentin)
This allows the dose levels of amoxicillin to be decreased and also increases the
Spectrum of activity.
The sulbactum is beta lactamase inhibitor, it act as suicide substrates for
Beta lactamase enzymes .
Sulbactum has a broader spectrum of activity against betalactamases than
Clavulanic acid but is less potent.
Sulbactum is combined with ampicillin for I.V (intravenous administration in a
Preparation called Unasyn.
Tazobactum is similar to sulbactum ,How ever its potency is more like clavulanic acid
It is administeted intravenously with piperacillin in a preparation called
Tazocin or Zosyn.
Sulbactum+ ampicillin = Unasyn.
Clavulanic acid+amoxycillin = Augmentin.
Tazobactumz+pieracillin = Tazocin or Zosyn.