Tetracyclines

Historical Background of Tetracyclines

• Discovered in 1948 from Streptomyces aureofaciens.
• Broad-spectrum antibiotic class.

Nomenclature of Tetracyclines

• Named after their four-fused cyclic structure.
• Examples:
  • Tetracycline
  • Doxycycline
  • Minocycline
  • Oxytetracycline
  • Chlortetracycline

Stereochemistry

• Four fused rings (hydronaphthacene nucleus).
• α-stereochemistry at C-4 is crucial for activity.

Structure-Activity Relationship (SAR)

• Hydroxyl and amine groups: Affect bacterial ribosome binding.
• Modifications at C-5, C-6, and C-7 influence:
  • Lipophilicity (affecting oral absorption).
  • Resistance to efflux pumps.
  • Protein binding.

Chemical Degradation Classification

• Epimerization at C-4: Leads to inactive 4-epitetracycline.
• Oxidative degradation: Produces toxic degradation products.
• Photodegradation: Especially in doxycycline (causes skin photosensitivity).

Important Products

• Tetracycline (prototype drug).
• Doxycycline (longer half-life, fewer GI effects).
• Minocycline (highly lipophilic, effective for acne).
• Tigecycline (glycylcycline, overcomes resistance).

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