The penicillin nucleus

The pharmacophore (part of a molecule that confers pharmacological activity) of penicillins is called the penicillin nucleus. It contains a β-lactam ring.

The β-lactam ring

The penicillin nucleus found in all penicillins contains a so-called β-lactam ring. This is a four-membered cyclic amide that is unstable in acidic or alkaline conditions. The small ring is under a great deal of strain, making the normally unreactive amide group more susceptible to hydrolysis, resulting in ring-opening to form open-chain compounds.

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  skeletal formula of the penicillin nucleus
• 
  ball-and-stick model of the penicillin nucleus
• 
  ball-and-stick model of the β-lactam ring
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  ball-and-stick model of clavulanic acid

β-lactamase inhibitors

β-Lactamase is an enzyme produced by certain penicillin-resistant bacteria. It inactivates penicillin antibiotics by disrupting their β-lactam ring. Once way to protect penicillins against β-lactamase is to modify their side chains − methicillin and flucloxacillin are examples of penicillins whose side chains make them β-lactamase resistant. Another tactic is to protect vulnerable penicillins with a β-lactamase inhibitor. These compounds, such as clavulanic acid, are not antibiotics, but they allow penicillin antibiotics to do their job by inhibiting β-lactamase.

Table of penicillins

Name	R group in side-chain	Natural/semi-synthetic	Uses/properties	Skeletal formula	3D model
benzylpenicillin penicillin G		natural	general infections, gonorrhoea and syphilis
flucloxacillin		semi-synthetic	controlling resistant Staphylococcus
penicillin F		natural	not used commercially
penicillin X		natural	not used commercially
penicillin K		natural	not used commercially
penicillin V		natural and semi-synthetic	general infections, ear, nose and throat
methicillin		semi-synthetic	controlling resistant Staphylococcus
ampicillin		semi-synthetic	lung and wound infections
amoxycillin		semi-synthetic	lung and urinary tract infections
carbenicillin		semi-synthetic	pneumonia, burns