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Natural antibiotics III
By : Noor hisham Al Atraqchi
M.Sc. pharmacognosy
Macrolides
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Macrolide antibiotics are typically characterized by macrocyclic
lactones having a ring-size ranging between 12-16 atoms and
also possess inherent extensive branching through the methyl
substituents.
However, the macrolactone ring essentially bears a glycosidal
linkage to either one or several sugar functions.
The various important members of ‘macrolide antibiotics’ are,
namely:
Erythromycin,
Clarithromycin,
Arithromycin,
Troleandomycin;
Spiramycins.
Macrolides
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MOA: The macrolides bind irreversibly to a site on the 50S subunit
of the bacterial ribosome, thus inhibiting translocation steps of
protein synthesis.
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In general, these antibiotics essentially exhibit a narrow spectrum of
antibacterial activity, most importantly against the Gram-positive
microorganisms.
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It is, however the antibacterial spectrum of the macrolides
resembles, but is not very much identical to, that of the penicillins;
hence, they are valuable alternative or substitute for such patients
who are found to be allergic to the penicillins.
Erythromycin
Biological Sources :
 It is produced by cultures Streptomyces erythreus .
 Waksman and Henrici were the pioneer in finding this antibiotic
in a soil sample collected from the Philippine.
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Erythromycin is, in fact, a mixture containing principally
Erythromycin A. Together with small quantum of Erythromycins
B and C.
Uses
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It is found to be most effective against Gram-positive
cocci.
A low concentration of erythromycin also inhibit
mycoplasma and the agent of Legionnaire’s disease.
It inhibits the spirochaete Treponema pallidum and is an
alternative to penicillin in the treatment of syphilis.
It is quite often regarded as the ‘drug-of-choice’ for
undiagnosed pneumonias.
It is extensively employed as an alternative to b-lactam
antibiotics in soft-tissue infections, skin and in respiratory
related diseases particularly in penicillin-allergic patients.
Aminoglycosides
Biological sources : Aminoglycosides are derived from either
Streptomyces species or Micromonospora species.
The term “aminoglycoside” stems from their structure—two
amino sugars joined by a glycosidic linkage to a central hexose
nucleus.
MOA: they inhibit protein synthesis by binding to the 30S
ribosomal subunit, where they interfere with assembly of the
functional ribosomal apparatus and/or cause the 30S subunit of
the completed ribosome to misread the genetic code
 The major spectrum of activity of the
aminoglycosides essentially comprise of aerobic
Gram-negative bacilli and Staphylococcus aurous.
The aminoglycoside antibiotics include the
following members :
 Amikacin,
 Gentamycin,
 Paramycin,
 kanamycin,
 Netilmicin,
 Streptomycin
 Tobramycin
Gentamycin
Biological Sources :It is an antibiotic complex produced by the fermentation
of Micromonospora purpurea and M. echinospora.
Uses
It is currently the most important drug of choice for the treatment of
infections caused by most aerobic Gram-negative bacteria, besides several
strains of Staphylococci.
2. It essentially exhibits a broad-spectrum antibacterial activity.
3. It is found to be specifically effective against Pseudomonas, because
species of this genus resistant to ‘other antibiotics’ have proved to be an
important cause of surgical infections.
4. It is employed topically in the treatment of impetigo, infected bed sores,
burns and also in the infections of external-eye.
Streptomycin
Biological Sources :
Streptomycin was obtained from a strain of
Streptomyces griseus and produced by the soil Actinomycete.
Uses
1. It is a potent antibacterial, and more so as a tuberculosstatic agent.
2. Streptomycin exerts its action in the control and management of Yersinia
pestis (plague) and tularemia.
3- streptomycin-penicillin used for endocarditis*; and streptomycintetracyclin employed for brucellosis.
4. Streptomycin exerts bacteriostatic action in low concentrations and
bactericidal in high concentrations to a good number of Gram-negative
and Gram-positive microorganisms.
Note: The incidence of serious auditory impairment is now recognized
Tetracyclines
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The tetracyclines are group of broad spectrum orally active
actinomycete antibiotics produced by cultures of Streptomyces
species, and possessing appreciable therapeutic value.
Chlortetracycline was the first member of this group isolated from
Streptomyces aureofaciens in 1948. .
MOA: the drugs bind reversibly to the 30S subunit of the bacterial
ribosome. This action prevents binding of tRNA to the mRNA–
ribosome complex, thereby inhibiting bacterial protein synthesis
‘methylation’ and ‘chlorination’ procedures have resulted in the
fermentative production of a good number of tetracycline variants,
namely:
demeclocycline,
methacycline,
doxycycline,
minocycline,
lymecycline
Tetracycline
Biological Source: It is obtained from Streptomyces species cultured
in an appropriate nutrient medium.
Preparation: It may be prepared by removal of chlorine from
chlortetracycline and subjecting it to hydrogenation.
Uses
 Tetracyclines are generally used in the treatment of infections of
the urinary tract and the intestines
 used in the treatment of infections caused by chlamydia, especially
in patients allergic to β- lactams and macrolides. However, their use
for these indications has decreased due to widespread development
of drug resistance to these compounds.
 Their most common current use is in the treatment of moderately
severe acne and rosacea.
 In addition, they may be used to treat Legionnaires’ disease.
Polypeptide Antibiotics
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A group of polypeptides of bacterial origin that are found to comprise of
D- and L-amino acids, do exert a marked and pronounced antibiotic
activity.
These specific antibiotics have two inherent major anomalies, namely:
first, very poor absorption from the intestinal tract; and
secondly, possess high degree of nephrotoxicity when used systemically.
Generally, the polypeptide antibiotics exert a predominantly Grampositive spectrum; however, there are a few-exceptions that are solely
active against Gram-negative organisms, such as: the strongly basic
polymyxins.
The various important members of ‘polypeptide antibiotics’ are,
namely:
cycloserine;
polymyxin-B;
colistin (polymixin-E),
bacitrasin;
Teichoplanin
Polymyxin B
Biological Source: Polymyxins represent a group of cycle
polypeptide antibiotics produced by various species of Bacillus.
However, polymyxins A to E were primarily isolated from Bacillus
polymyxa .
MOA:
Polypeptide antibiotics act by binding to phospholipids on the bacterial
cell membrane of gram-negative bacteria. They have a detergent-like
effect that disrupts cell membrane integrity, leading to leakage of cellular
components and ultimately cell death.
uses
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2.
It is used topically in ointments (usually 5000 or
10,000 Units/g) and ophthalmic solutions (10,000
Units/ml).
It is used topically either for the treatment or the
prevention and treatment of external ocular infections
caused by susceptible microorganisms, especially Ps
aeruginosa.