Aminoglycoside Antibiotics

Study Notes

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.

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.

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

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.

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.

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.

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