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