Aminoglycosides: Streptomycin, Neomycin, Kanamycin

1. AMINOGLYCOSIDES:
Streptomycin, Neomycin,
Kanamycin

2. Introduction
Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative
antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule
an amino-modified glycoside (sugar).
The term can also refer more generally to any organic molecule that contains amino sugar
substructures.

3. Aminoglycoside antibiotics display bactericidal activity against Gram-negative aerobes and
some anaerobic bacilli where resistance has not yet arisen but generally not against Gram-
positive and anaerobic Gram-negative bacteria.
The first aminoglycoside, streptomycin, was isolated in 1943 from Streptomyces griseus by
Albert Schatz and Selman A. Waksan (reported in 1944).

4. It was a seminal discovery in the history of antibiotics since streptomycin was the first
effective treatment for tuberculosis as well as the first useful antibiotic derived from a
bacterial source.
Streptomycin lacks the common 2-deoxystreptamine moiety present in most other members of
this class. Other examples include the deoxystreptamine-containing agents kanamycin,
tobramycin, gentamicin, and neomycin.

5. 2-Deoxystreptamine

7. Classification
(A) 4,6-Disubstitutedaminoglycosides
(B) 4,5-Disubstitutedaminoglycosides
(C) Spectinomycin

13. Streptomycin

14. Aminoglycosides that are derived from bacteria of the Streptomyces genus
are named with the suffix -mycin, whereas those that are derived from
Micromonospora are named with the suffix -micin.

15. Mechanism of action
Aminoglycosides binds to specific 30S-subunit ribosomal proteins. Protein synthesis is
inhibited by them in at least three ways:
①They block the formation of initiation 70S ribosomal mRNA complex;
②They induce misreading of mRNA causes incorporation of incorrect amino acids into
peptide resulting in a non-functional or abnormal protein synthesis.
③ They inhibit the combination of the releasing factor with the site A on ribosome prevent the
synthesized peptide chain releasing from the 70S ribosomal mRNA complex and the 70S
ribosomal mRNA complex dissociating into 30S and 50S subunits.

18. Video:
https://www.youtube.com/watch?v=h1d2meyYpOE
https://www.youtube.com/watch?v=1qZA-pG_zMA

22. SAR
The aminoglycosides consist of two or more amino sugars joined in glycoside linkage to a
highly substituted 1,3-diaminocyclo hexane (aminocyclitol), which is a centrally placed ring.
The ring is a 2-deoxy streptamine in all aminoglycosides except streptomycin and
dihydrostreptomycin, where it is streptidine.
 In kanamycin and gentamycin families, two amino sugars are attached to 2-deoxy
streptamine.
 In streptomycin, two amino sugars are att
ached to strepidine.
 In neomycin family, there are amino sugars attached to 2-deoxy streptamine.

23. - 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.
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.

24. Centrally placed hexose ring (aminocyclitol ring)

25. 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.
https://www.youtube.com/watch?v=JbHp7CAyldc
https://www.youtube.com/watch?v=ffZpkYHOxTg