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β-Lactam Antibiotics

Updated: Mar 28

Historical Background of β-Lactam Antibiotics

  • Discovered in 1928 by Alexander Fleming (Penicillin).

  • First widely used antibiotic class.

  • β-Lactam antibiotics revolutionized bacterial infection treatment.

Nomenclature

  • Named after the β-lactam ring, a four-membered cyclic amide.

  • Subclasses:

    1. Penicillins (e.g., Penicillin G, Amoxicillin)

    2. Cephalosporins (e.g., Ceftriaxone, Cefuroxime)

    3. β-Lactamase inhibitors

    4. Monobactams (e.g., Aztreonam)

Stereochemistry

  • Penicillins have a fused bicyclic system (thiazolidine + β-lactam), affecting their stability and reactivity.

  • Cephalosporins have a dihydrothiazine ring, increasing resistance to β-lactamases.

  • Carbapenems have a unique stereochemistry with a trans configuration at C-5 and C-6, enhancing activity.

Structure-Activity Relationship (SAR)

  • Essential β-lactam ring: Responsible for antibacterial activity by inhibiting bacterial transpeptidases (PBPs).

  • The side chain (R group) affects:

    • Spectrum of activity.

    • Resistance to β-lactamases.

    • Pharmacokinetics (e.g., oral vs. IV).

  • Modifications in the thiazolidine/dihydrothiazine ring impact stability and activity.

Chemical Degradation Classification

  • Hydrolysis by β-lactamases: Leads to inactive penicilloic acid.

  • Acid hydrolysis: Common in penicillins (unstable in acidic pH).

  • Oxidative degradation: Occurs in some cephalosporins.

  • Ring opening: Leads to inactivation.

Important Products

  • Penicillin G (natural).

  • Amoxicillin, Ampicillin (semi-synthetic, broad-spectrum).

  • Cephalexin, Ceftriaxone (cephalosporins).

  • Imipenem, Meropenem (carbapenems).

  • Aztreonam (monobactam).


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