Structural features of aminoglycoside antibiotics

The aminoglycoside antibiotics contain two important structural features. They are amino sugar portion and centrally placed hexose ring, which is either 2-deoxystreptamine or streptidine.

1. Amino sugar portion

i. The bacterial inactivating enzymes targets C-6 and C-2 position, and the substitution with methyl group at C-6 increases the enzyme resistance.

ii. Cleavage of 3-hydroxyl or the 4-hydroxyl or both groups does not affect the activity.

2. Centrally placed hexose ring (aminocyclitol ring)

i.Various modifications at C-1 amino group have been tested. The acylation (e.g. amikacyn) and ethylation (e.g. 1-N-ethylsisomycin) though does not increase the activity helps to retain the antibacterial potency.

ii. In sisomicin series, 2-hydroxylation and 5-deoxygenation result in the increased inhibition of bacterial inactivating enzyme systems. Thus, very few modifications of the central ring are possible, which do not violate the activity spectrum of aminoglycosides.