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SULBACTAM -BETALACTAMASE INHIBITOR,INTRODUCTION,MECHANISM OF ACTION,SAR,SYNTHESIS, USES

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

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SULBACTUM
Prof.P.Ravisankar
Vignan Pharmacy college
Valdlamudi
Guntur Dist.
Andhra Pradesh
India
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
SULBACTAM -BETALACTAMASE INHIBITOR,INTRODUCTION,MECHANISM OF ACTION,SAR,SYNTHESIS, USES
SULBACTAM -BETALACTAMASE INHIBITOR,INTRODUCTION,MECHANISM OF ACTION,SAR,SYNTHESIS, USES
SULBACTAM -BETALACTAMASE INHIBITOR,INTRODUCTION,MECHANISM OF ACTION,SAR,SYNTHESIS, USES
SULBACTAM -BETALACTAMASE INHIBITOR,INTRODUCTION,MECHANISM OF ACTION,SAR,SYNTHESIS, USES

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SULBACTAM -BETALACTAMASE INHIBITOR,INTRODUCTION,MECHANISM OF ACTION,SAR,SYNTHESIS, USES

  • 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. -
  • 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.