Beta Lactamase inhibitor sulbactum is beta lactum structure that haveNegligible antibacterial activity but inhibit beta lactamases.Sulbactum can be administered alongside penicillins to protect them fromBeta lactamases and to broaden their spectrum of activity.Betalactamase inhibitors areClavulanic acidTazobactum
*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 formingirreversible complexes with beta-lactamase, which inactivates the enzyme, and as aresult 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 bybacteria 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-carboxylate4,4-dioxide.*Its chemical formula is C8H10NNaO5S*molecular weight of 255.22.*The structural formula ofsulbactum is:Chemistry of sulbactum:
No acylamino side chain at6th positionBeta lactum ringFree corboxylate essentialBicyclic systemIs importantSulbactum mechanism is based on irreversible inhibitor and could be classed as aSuicide substrate.The drug fits the active site of betalactamase, and the beta lactum ring is opened bySerine residue . The acyl-enzyme intermediate then reacts further with another enzymaticNucleophilic group(possibly NH2 ) to bind the drug irreversibly to the enzyme.Sulfone group is essential and alsoEnhances the activity.The corbonyl on theBetalactum at position -7 is mustN at position 1Is must for activity.Methyl groups atPosition 3 are requiredFor activty.SAR (structure activity relationship )of Sulbactum
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 atomresults in an inactive compound.6.Removal of ketone bonds results in a new compound with reduced activityor 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.-
Most beta lactamases and as such is now used in combination with traditionalPencillins such as amoxicillin(+ Clavulanic acid Augmentin)This allows the dose levels of amoxicillin to be decreased and also increases theSpectrum of activity.The sulbactum is beta lactamase inhibitor, it act as suicide substrates forBeta lactamase enzymes .Sulbactum has a broader spectrum of activity against betalactamases thanClavulanic acid but is less potent.Sulbactum is combined with ampicillin for I.V (intravenous administration in aPreparation called Unasyn.Tazobactum is similar to sulbactum ,How ever its potency is more like clavulanic acidIt is administeted intravenously with piperacillin in a preparation calledTazocin or Zosyn.Sulbactum+ ampicillin = Unasyn.Clavulanic acid+amoxycillin = Augmentin.Tazobactumz+pieracillin = Tazocin or Zosyn.