Aminoglycoside Antibiotics

Aminoglycoside Antibiotics

• Aminoglycoside is a category of traditional Gram-negative antibacterial therapeutic agents that inhibit protein synthesis and contain an amino-modified glycoside (sugar) as a portion of the molecule.
• The term also refers to any organic molecule that contains amino-sugar substructures.

Structure and Characteristics

• Aminoglycoside antibiotics contain one or more amino sugars linked to an aminocytitol ring by glycosidic bonds.
• They display bactericidal activity against Gram-negative aerobes and some anaerobic bacilli, but have limited activity against Gram-positive and anaerobic Gram-negative bacteria.

Adverse Effects

• Aminoglycoside antibiotics can produce severe adverse effects, including nephrotoxity, ototoxicity, and neuro effects, which have limited their use to serious systemic indications.

Mode of Action

• Aminoglycosides exhibit bactericidal effects due to ribosomal binding on 30s and 50s subunits as well as the interface, producing misreading and disturbing normal protein synthesis.
• Cell membrane damage also plays an integral part in ensuring bacterial cell death.

Examples of Aminoglycoside Antibiotics

• Streptomycin (source: Streptomyces griseus)
• Neomycin (source: S. fradiae)
• Kanamycin (source: S. kanamyeleticus)
• Gentamycin (source: Micromonospora purpura)
• Netilmicin (source: Micromonospora species)
• Tobramycin (source: S. tenebrarius)
• Framycetin (source: S. decaris)
• Paromomycin (source: S. rimosus and S. paramomycinus)
• Amikacin (1-L-(-) 4-amino-2-hydroxy butyryl kanamycin)

Individual Antibiotics

• Streptomycin: used in the treatment of infections caused by gram-negative bacteria, particularly P. aeruginosa, and has a high degree of activity against burned skin.
• Neomycin: used in the treatment of ear, eye, and skin infections, including burns, wounds, ulcer, and infected dermatoses, but is photosensitive.
• Kanamycin: use is restricted to infections of the intestinal tract and systemic infections, and does not possess a D-ribose molecule.
• Tobramycin: has similar activity to gentamycin, and is useful in the treatment of bacterial osteomyelitis and pneumonia caused by Pseudomonas species.

Structure-Activity Relationship (SAR) of Aminoglycoside Antibiotics

• Aminoglycosides consist of two or more amino sugars joined in glycoside linkage to a highly substituted 1,3-diaminocyclohexane (aminocyclitol) ring.
• The ring is a 2-deoxy streptamine in all aminoglycosides except streptomycin and dihydrostreptomycin, where it is streptidine.
• Amino sugar portion:
  • Bacterial inactivating enzymes target C-6 and C-2 positions, and substitution with a methyl group at C-6 increases enzyme resistance.
  • Cleavage of 3-hydroxyl or the 4-hydroxyl or both groups does not affect the activity.
• Centrally placed hexose ring (aminocyclitol ring):
  • Various modifications at C-1 amino group have been tested, with acylation (e.g., amikacyn) and ethylation (e.g., 1-N-ethylsisomycin) helping to retain antibacterial potency.

Learn about aminoglycoside antibiotics, their structure, characteristics, and bactericidal action as Gram-negative antibacterial therapeutic agents.