This document discusses several macrolide antibiotics, including erythromycin, clarithromycin, azithromycin, chloramphenicol, and clindamycin. It describes their mechanisms of action, which involve inhibiting bacterial protein synthesis by binding to the 50S ribosomal subunit. It provides details on their isolation, chemical structures, stability, formulations, and common medical uses for treating bacterial infections.

1. MACROLIDE
Raj K. Prasad (Gold Medalist)
M. Pharm. (Pharmaceutical Chemistry)

2. MACROLIDE
•Macrolide antibiotics inhibit bacterial
protein synthesis.
•Macrolides contain a many-membered
lactone ring (14 for erythromycin and
clarithromycin and 15 for azithromycin) to
which are attached to one or more deoxy
sugars.

3. Mechanism of Action
• Erythromycin apparently inhibits
the translocation step wherein
the nascent peptide chain
temporarily residing at the A site
of the transferase reaction fails
to move to the P, or donor, site
by binding reversibly to the 50S
ribosomal subunits of sensitive
organisms.

4. ERYTHROMYCIN
 Isolation of erythromycin
occurred from Streptomyces
erythraeus.

5. Stability of Erythromycin
•Erythromycin is unstable to stomach acids, but can be
taken orally in a coated tablet dosage form.
•The acid sensitivity of erythromycin is due to the presence
of a ketone and two alcohol groups which are set up for the
acid-catalysed intramolecular formation of a ketal.

6. How to prevent instability?
•Preventing this, is to protect the hydroxyl groups.
For example, clarithromycin is a methoxy analogue
of erythromycin which is more stable to gastric
juices and has improved oral absorption.
•Another method of increasing acid stability is to
increase the size of the macrocycle to a 16-
membered ring.

7. Uses
•Erythromycin is used for bacterial infections
such as diphtheria,
•whooping cough, tonsillitis, otitis, sinusitis,
pneumonia, gonorrhea, and so on.
•It is the drug of choice for pneumonia,
diphtheria, enteritis, and so on.

8. CLARITHROMYCIN
 The simple methylation of the
6-hydroxyl group of
erythromycin creates a
semisynthetic derivative that
fully retains the antibacterial
properties of the parent
antibiotic.

9. AZITHROMYCIN
 Azithromycin contains a 15-membered
macrocycle where an N -methyl group has
been incorporated between carbons 9 and
10 and the carbonyl moiety of macrocycle.
 It is one of the world’s best-selling drugs.
 It is used for treating bacterial bronchitis,
pneumonia, skin, and sexual infections.

10. CHLORAMPHENICOL
 It was first isolated from a
culture fluid of the
actinomycete Streptomyces
venezuelae; however, it is
only currently produced
synthetically.

11. Synthesis of Chloramphenicol

12. Mechanism of Action
• The drug prevents the binding of
the amino acid–containing end of
the aminoacyl tRNA to the
acceptor site on the 50S ribosomal
subunit.
• The interaction between peptidyl-
transferase and its amino acid
substrate is blocked, inhibiting
peptide bond formation.

13. USES
•It is the drug of choice for treating typhoid fever,
and it is used for treating brain swellings.
•It was the drug of choice for therapy of bacterial
meningitis in children (in combination with
ampicillin).

14. CLINDAMYCIN
 A very water-insoluble palmitate
hydrochloride prodrug of clindamycin is
also available (lacks bitter taste).
 Clindamycin phosphate is the 5-
phosphate ester of clindamycin which is
intended for parenteral (intravenous or
intramuscular) administration for the
treatment of serious infections and
instances when oral administration is
not feasible.

15. Uses
•Clindamycin is recommended for the
treatment of a wide variety of upper
respiratory, skin, and tissue infections caused
by susceptible bacteria.