Aminoglycosides

Historical Background of Aminoglycosides

• First discovered in 1944 (Streptomycin by Selman Waksman).
• Used mainly for Gram-negative infections and tuberculosis.

Nomenclature of Aminoglycosides

• Contain amino sugars linked by glycosidic bonds.
• Common names:
  • Streptomycin
  • Neomycin
  • Kanamycin

Stereochemistry

• Multiple chiral centers in aminosugar moieties.
• The specific orientation of hydroxyl and amino groups affects activity and bacterial binding.

Structure-Activity Relationship (SAR)

• 1,3-diaminoinositol core: Essential for ribosomal binding.
• Aminosugar modifications:
  • Improve ribosome binding.
  • Influence resistance to modifying enzymes.
• Hydroxyl and amine groups interact with rRNA, causing misreading of mRNA.

Chemical Degradation Classification

• Oxidative degradation: Leads to inactive products.
• Enzymatic modification: By bacterial enzymes (acetylation, phosphorylation).
• Hydrolysis in acidic conditions.

Important Products

• Streptomycin (first discovered, used for TB).
• Gentamicin (broad-spectrum use).
• Amikacin (resistant to aminoglycoside-modifying enzymes).
• Neomycin (topical use).

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