Macrolides: Properties, Synthesis and Applications / Edition 1

by Biljana Arsic, Predrag Novak, Goran Kragol, Jill Barber, Maria Grazia Rimoli

Overview

Macrolide antibiotics represent a class of natural macrocyclic products, one of the most clinically important antibiotics. Unfortunately, the production and development of new macrolide antibiotics are not represented enough in the pharmaceutical industry today. The intention of the book is therefore not only to be a teaching tool for students and experts, but also to draw the attention of the general public to this extremely useful, cheap and relatively unharmful effective anti-macrobials, and potential anti-malarials. The authors introduce the different classes of macrolides and their derivatives, principles of their biological activity, their structure and interactions with biological targets as well as synthetic methods to produce new macrolide antibiotics of similar or improved properties. Special emphasis was put on conjugates of macrolides with nucleobases or nucleosides with numerous applications; among them the most important remains the attempt to overcome bacterial resistance.

Product Details

ISBN-13:	9783110515022
Publisher:	De Gruyter
Publication date:	03/19/2018
Pages:	112
Product dimensions:	6.69(w) x 9.45(h) x (d)
Age Range:	18 Years

About the Author

Macrolide antibiotics represent a class of natural macrocyclic products, one of the most clinically important antibiotics. Unfortunately, the production and development of new macrolide antibiotics are not represented enough in the pharmaceutical industry today. The intention of the book is therefore not only to be a teaching tool for students and experts, but also to draw the attention of the general public to this extremely useful, cheap and relatively unharmful effective anti-microbials, and potential anti-malarials. The authors introduce the different classes of macrolides and their derivatives, principles of their biological activity, their structure and interactions with biological targets as well as synthetic methods to produce new macrolide antibiotics of similar or improved properties. Special emphasis was put on conjugates of macrolides with nucleobases or nucleosides with numerous applications; among them the most important remains the attempt to overcome bacterial resistance.

Biljana Arsic, University of Nis, Nis, Republic of Serbia.

Table of Contents

Preface v

1 The macrolide antibiotics and their semi-synthetic derivatives 1

1.1 What happens to macrolides in the stomach? The effect of acid on the erythromycins and their derivatives 3

1.2 Crystal structures of macrolide antibiotics bound to bacterial ribosomes 9

1.3 Mode of action of macrolide antibiotics 10

1.3.1 Binding of azithromycin 13

1.4 Investigation of kinetics of macrolide interaction with ribosomes and possible models for different forms in binding to bacterial ribosomes 15

1.5 Solution state structures of free and bound macrolide antibiotics 17

References 24

2 The semisynthetic routes towards better macrolide antibiotics 31

2.1 Introduction 31

2.2 Erythromycin 31

2.3 Second generation of macrolide antibiotics 34

2.3.1 Roxithromycin 34

2.3.2 Clarithromycin 35

2.3.3 Azithromycin 38

2.3.4 Clarithromycin/azithromycin hybrids 42

2.4 The third generation of macrolide antibiotics 44

2.4.1 Telithromycin (HMR3647) 47

2.4.2 Cethromycin (ABT773) 49

2.4.3 Solithromycin (CEM101) 53

2.4.4 Other ketolides: TE-802, modithromycin (EDP-420) 53

2.5 Antibacterial macrolide hybrids - next generations of macrolide antibiotics 56

2.5.1 Macrolide conjugates 57

2.5.2 Macrolide merged hybrids 57

2.5.3 Macrolactone ring reconstruction 59

2.6 Conclusion 60

References 61

3 Interactions of macrolides with their biological targets 63

References 73

4 Hybrids of macrolides and nucleobases or nucleosides: synthetic strategies and biological results 79

4.1 Macrolide hybrid compounds: an excellent approach 79

4.2 Macrolide antibiotic resistance 80

4.3 How and why to conjugate macrolides to nucleobases or nucleosides: introduction 80

4.3.1 Nucleobases or nucleosides conjugates with erythromycin and azithromycin 81

4.3.1.1 Introduction 81

4.3.1.2 Synthesis 81

4.3.1.3 Biological results 83

4.3.2 Clarithromycin-adenine and related conjugates 83

4.3.2.1 Introduction 83

4.3.2.2 Synthesis 83

4.3.2.3 Biological results 87

4.4 Novel spiramycin-like conjugates: synthesis and antibacterial and anticancer evaluations 88

4.4.1 Introduction 88

4.4.2 Synthesis 90

4.4.3 Antibacterial studies 91

4.4.4 Anticancer studies 92

References 94

Index 101