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