Miscellaneous Antibiotics – Medicinal Chemistry III B. Pharma 6th Semester

Miscellaneous Antibiotics

Contents

• Structure and uses of chloramphenicol, novobiocin and
vancomycin

• Synthesis of chloramphenicol

Learning
Objectives

At the end of this lecture, student will be able to

• Write the structure of chloramphenicol

• List the clinical applications of chloramphenicol,
novobiocin and vancomycin

• Outline the synthesis of chloramphenicol

Introduction

• Among the many hundreds of antibiotics that have been
evaluated for activity

• Several have gained significant clinical attention but do
not fall into any of the previously considered groups

• Some of these have quite specific activities against a
narrow spectrum of microorganisms

• Some have found a useful place in therapy as substitutes
for other antibiotics to which resistance has developed

List of
Some Miscellaneous Antibiotics

• Chlormphenicol

• Vancomycin

• Novobiocin

Chloramphenicol

• Isolated from S.venezuelae

• Widely used broad-spectrum antibiotic

• From streptomyces venezuelae an organism found in a sample
of soil collected in Venezuela

• Chloramphenicol  
possesses   two   chiral  
carbon   atoms   in  
the acylamidopropanediol chain.

• Biological activity resides almost exclusively in the
d-threo isomer the L-threo

• D- and L-erythro isomers are virtually inactive

Mechanism of Action

• Chroramphenicol binds to the 50S ribosomal subunit and
inhibit the peptidyl transferase activity. So no new peptide bonds are formed-
thereby inhibiting protein synthesis

• Recommended specifically for the treatment of serious
infections caused by strains of gram positive and gram-negative bacteria that
have developed resistance to penicillin G and ampicillin, such as H.
Influenzae, salmonella typhi, S. Pneumoniae, B. Fragilis, and N. Meningitidis

• Penetration into the central nervous system

• Alternative therapy for meningitis

• Not recommended for the treatment of urinary tract
infections

• 5% to 10% of the unconjugated form is excreted in the
urine

• Treatment of rickettsial infections such as Rocky Mountain
spotted fever

• Is bitter this antibiotic is administered orally either in
capsules or as the palmitate ester

Synthesis of
Chloramphenical

Novobiocin

• Novobiocin has a unique structure among antibiotics

• Possesses a glycosidic sugar moiety

• The sugar in novobiocin devoid of its carbamate ester, has
been named noviose

• Is an aldose with the configuration of l-lyxose

• The aglycon moiety has been termed novobiocic acid

• Inhibit bacterial protein and nucleic acid synthesis

• Bind to the subunit of DNA gyrase

• Interfere with DNA supercoiling276 and energy transduction
in bacteria

• Treatment of staphylococcal infections resistant to other
antibiotics and sulfas and for patients allergic to these drugs

• Shortcoming 
that  limits  the 
usefulness  of  novobiocin 
is  the relatively  high 
frequency  of adverse reactions,
such as urticaria, allergic rashes, hepatotoxicity, and blood dyscrasias

Vancomycin

• Vancomycin inhibits cell wall synthesis by preventing the
synthesis of cell wall mucopeptide polymer

• Binding with the d-alanine-d-alanine terminus of the
uridine diphosphate-n-acetylmuramyl peptides required for mucopeptide
polymerization

Summary

• Biological activity of chloramphenicol resides almost
exclusively in the d-threo isomer the L-threo

• Chloramphenicol is used in the treatment of rickettsial
infections such as Rocky Mountain spotted fever

• Novobiocin Bind to the subunit of DNA gyrase

• Vancomycin inhibits cell wall synthesis by preventing the
synthesis of cell wall mucopeptide polymer

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