β-Lactam antibiotics are characterized by a four-membered ring structure called a β-lactam ring, which is essential for their antibacterial activity.
Historical Background:
The discovery of β-lactam antibiotics began with the serendipitous finding of penicillin by Alexander Fleming in 1928.
Since then, many additional β-lactams have been discovered or synthesized.
Nomenclature:
The name β-lactam refers to the presence of a chemical structure known as a β-lactam ring.
Specific subclasses (like penicillins, cephalosporins, monobactams, and carbapenems) have their own nomenclature rules.
Stereochemistry:
The stereochemistry of β-lactam antibiotics varies between subclasses and individual compounds.
A common feature is the four-membered β-lactam ring, which is usually fused to another ring structure.
Structure-Activity Relationship:
This class of antibiotics includes penicillins, cephalosporins, monobactams, and carbapenems.
The key feature of all β-lactam antibiotics is the β-lactam ring structure:
1.The β-Lactam Ring:
This is a highly strained and reactive four-membered ring.
Its strain and reactivity are key to its antibiotic activity, as it allows the drug to bind to and inhibit bacterial enzymes known as penicillin-binding proteins (PBPs) involved in the synthesis of the peptidoglycan layer of the bacterial cell wall, leading to cell lysis and death.
2.Side Chains:
The side chains attached to the β-lactam ring play a critical role in the antibacterial activity, stability, and resistance to β-lactamases, the enzymes that many bacteria produce to resist β-lactam antibiotics.
For example, methicillin, a penicillin derivative, is resistant to β-lactamase due to a bulky side chain that prevents the enzyme from reaching the β-lactam ring.
Chemical Degradation:
Many β-lactam antibiotics can be degraded by bacterial β-lactamase enzymes, leading to antibiotic resistance.
They can also undergo hydrolysis under certain conditions.
Important Products:
Some important β-lactam antibiotics include penicillin G, amoxicillin, cephalexin, ceftriaxone, meropenem, and aztreonam.
