‫ووصينا اإلنسان بوالديه إحسانا‬

‫بسم اهلل الرحمن الرحيم‬

amino glycoside
 INTRODUCTION
Selman Waksman’s commitment to the
isolation and screening of soil bacteria
in the search for bioactive small molecules,
especially potential antibiotics,
was validated by the discovery of
streptomycin.
Although streptomycin was not the
first antibiotic (penicillin, a fungal
product,
had been isolated some years earlier),
its discovery was a landmark in
.antibiotic history
It was the first effective therapeutic for
,tuberculosis

a disease that had

terrorized humans for centuries and a cause
of human morbidity and mortality
.unmatched by wars or any other pestilence
Streptomycin was the first aminoglycoside
to be identified and characterized and is
noteworthy in being the first useful
antibiotic isolated from a bacterial source.
Following on the discovery of streptomycin
and its streptamine-based relatives a new
generation of the aminoglycosides derived
from
deoxystreptamine (DOS) was not long in–2
coming
 Waksman and Fleming could be considered the fathers of chemical
biology

The founders of the antibiotic era: Selman Waksman (discoverer of

streptomycin) in 1944
. and Alexander Fleming (discoverer of penicillin) in 1928
.Streptomycin brought Waxman the Noble prize in 1952
The structural relationships of the streptamine
.family of antibiotics
The structural relationships of the 2-deoxystreptamine family
.of antibiotics
 Other Classes of Aminoglycoside-
Aminocyclitol Antibiotics
Ashimycin
Astromicin/Istamycin
Boholmycin
Kasugamycin
Myomycin
Spectinomycin
Trehalosamine
Validamycin
Neomycin family- Framycetin, Paromomycin
 -: Definition of amino glycoside
A group of antibiotics that inhibit bacterial -
protein synthesis and are particularly active
.against Gram-negative bacteria

Any of a group of broad-spectrum antibiotics, - -

such as streptomycin, derived from species of
Streptomyces or Micromonospora bacteria and
used to treat infections caused by gram-negative
.bacteria
Antibiotics contain an aminocyclitol moiety to which aminosugars are -
glycosidically linked. They may be more correctly called aminocyclitol
.antibiotics

Cyclohexanes with several substituted or unsubstituted amino and -

.hydroxyl groups which bring them high water solubility
 Chemistry and Sources of aminoglycoside

An aminoglycoside is a molecule or a portion of a molecule composed of

an aminocyclitol moiety to which aminosugars are glycosidically linked
Aminoglycosides that are derived from
bacteria of the Streptomyces genus are named with the suffix –mycin
 ,neomycin, They  are a group of antibiotics . They include amikacin , gentamicin, kanamycin
 netilmicin , paromomycin , streptomycin, and tobramycin . Those which are derived from
 species are named with the suffix -mycin, while those which are derived from Streptomyces
.are named with the suffix -micin micromonospora
Arbekacin, a Semi synthetic Aminoglycoside

The aminocyclitols are compounds related to cyclitols. They possess features of

relative and absolute configuration that are characteristic of their class and have been
extensively studied; but these features are not clearly displayed by general methods of
stereochemical nomenclature, so that special methods of specifying their configuration
are justified and have long been used. In other than stereochemical respects, their
.organic chemistry nomenclature should follow the general rules of
The aminocyclitol family of natural products is a class of sugar-derived microbial
secondary metabolites that demonstrate significant biological activities.
Aminocyclitols are a major component of aminoglycoside antibiotics.
 SAR of aminoglycosides
ANT-4'' OH
APH- 3'
6'' ANT-4'
4''
5'' O AAC- 2' OH
4'
HO ' 3'
H2N 2 OH
2'' 1'' OH
3'' 6 O
5 H2N
5' 6' NH2
HO III 4
O
1 ' I
O
H2N 1 2
'' '' NH2
ANT-2 , APH-2 3
II AAC- 6'
AAC- 3
Kanamycin B

-: Is contain as general , three rings , very important

Two rings as aminohexose *
. Other one is aminocyclitols *
 SAR of aminoglycosides
ANT-4'' OH
APH- 3'
6'' ANT-4'
4''
5'' O AAC- 2' OH
4'
HO ' 3'
H2N 2 OH
2'' 1'' OH
3'' 6 O
5 H2N
5' 6' NH2
HO III 4
O
1' I
O
H2N 1 2 NH2
ANT-2'', APH-2'' 3
II AAC- 6'
AAC- 3
Kanamycin B

Is depended as general on interaction of Aminoglycoside

Deactivating enzymes produce from bacteria ( AAC ,
APH , ANT ) with OH or NH2 groups on rings of
. aminoglycosides , but not all
 SAR of aminoglycosides
.Ring 1 :- have four sites interaction with R.Factor
. At C2 & C6 NH2 Groups interaction with AAC
Must be changes but without remove its , because its necessary
-: to antibacterial activity . Can change as
. C2 NH2 to secondary or tertiary amine *
Methyltion of C6 NH2 *
. Due to Increase resistance against AAC
. At C3 & C4 OH Groups interaction with APH & ANT
. Can lack to resistance against APH & ANT
 SAR of aminoglycosides
Ring 2 :- one site in this ring if change due to increase
. resistance against deactivating enzymes to much
. By change C1 to amide group in amikacin
6' 2-Deoxystreptamine
H 2NH2C
5' O
HO 4'
HO 1'
3' 2' H 2N
O OH
OH 2
O 3
4 NH C C CH 2 CH 2 NH 2
2
5 6 1 H
HO O
Kanosamine 5''
6'' 1''
HOH2C O OH
HO
4'' 3'' 2''
NH2

Amikacin, L-AHBA derivative of

Kanamycin A
 SAR of aminoglycosides

. Ring 3 :- has limited changes

In C2 & C3 can changes to NH2 primary or
. secondary amine
. In C4 can change to axial or equatorial
Due to more resistance against aminoglycosides
. deactivating enzymes
 Mechanism of action
. Binding with bacterial 30S ribosomal subunit

Aminoglycosides have several potential antibiotic mechanisms, some as

protein synthesis inhibitors, although their exact mechanism of action is
-: not fully known, Can cusing
increased rate of error in synthesis with premature termination *.
ribosomal translocation inhibition of *
. disrupt the integrity of bacterial cell membrane *

. This is very short , the details in my head

 Micronomicin
treatment of
infection caused by gram-negative
bacteria such as Pseudomonas
.aeruginosa, bacillus coli
 Verdamicin
Verdamicin is an amino glycoside antibiotic
.Micromonospora grisea produced by
Hygromycin B
 Geneticin-G418
is an aminoglycoside antibiotic similar in
structure to gentamicin B1. It is
produced by Micromonospora
‘ .rhodorangea
 Capreomycin
Capreomycin is a peptide antibiotic, commonly grouped with the
aminoglycosides, which is given in combination with other
antibiotics for tuberculosis. Adverse effects include
.nephrotoxicity and 8th cranial nerve toxicity
The drug should not be given with streptomycin or other drugs
.that may damage the 8th nerve
.It is a cyclic peptide
Apramycin
Apramycin (also Nebramycin II) is an
aminoglycoside antibiotic used in veterinary
.medicine
 Pharmaceutical Look on
aminoglycoside antibiotics
Preparations
• Streptomycin sulphate injection
• Kanamycin sulphate injection
• Neomycin sulphate cap
• Gentamicin sulphate injection
• Tobramycin injection
• Amikacin injection
• Netilmicin injection
• Paromomycin cap
• Framycetin ointment, cream or
solution
 Antimicrobial activity
.broad-spectrum antibiotics •
.Gram –ve bacilli •
Enterobacteria – E.coli , Klebsiella , Shigella •
Pneumonia and urinary infections •
.Haemophilus and Neisseria •

Mycobacterium tuberculosis •
G(+) and G(-) aerobic cocci except staphylococci and •
.anaerobic bacteria are less susceptible
 Common side effects:-
- unsteadiness,.
- changes in urine output.
- loss of appetite.
- increased thirst.
- muscle twitching.
- nausea and vomiting.
- numbness of the mouth or face.
- convulsions and fever can occur.
 Less common side effects:-
- skin rash.
- fever.
- chills, shaking.
- drowsiness.
-trouble breathing and weakness
 A less common side effect:-
- loss of vision (Ototoxicity)
•Aminoglycosides can damage a person's inner ear or auditory
nerve causing "ear poisoning." This damage can be permanent.
Symptoms of ear damage include hearing loss, unsteadiness,
feeling of ear fullness, dizziness, unable to tolerate head
movement and lightheadedness. Reversible Once treatment is
stopped Back to normal.
- kidney toxicity (Nephrotoxicity)
• is usually reversible upon discontinuation of the medication.
Symptoms of kidney toxicity may not be noticeable, but can
include decrease urination, thirst, increased heart rate,
dizziness and decreased appetite.