Tetracyclines

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Historical Background of Tetracyclines

• Discovered in 1948 from Streptomyces aureofaciens.

• Broad-spectrum antibiotic class.

Nomenclature

• 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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