Chemistry of Antibiotics and Related Drugs

227 Pages·2016·11.57 MB·English

by  Mrinal K. Bhattacharjee (auth.)

Mrinal K. Bhattacharjee
Chemistry of
Antibiotics
and Related
Drugs
Chemistry of Antibiotics and Related Drugs

Mrinal K. Bhattacharjee
Chemistry of Antibiotics
and Related Drugs
Mrinal K. Bhattacharjee
Department of Chemistry
and Biochemistry
Long Island University
Brooklyn , NY , USA
ISBN 978-3-319-40744-9 ISBN 978-3-319-40746-3 (eBook)
DOI 10.1007/978-3-319-40746-3
Library of Congress Control Number: 2016944926
© Springer International Publishing Switzerland 2016
T his work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of
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does not imply, even in the absence of a specifi c statement, that such names are exempt from the relevant
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Printed on acid-free paper
This Springer imprint is published by Springer Nature
The registered company is Springer International Publishing AG Switzerland
This book is dedicated to my wife Nayana
and daughter Neha

Pref ace
This book discusses the various classes of antibiotics and their mechanisms of action.
Millions of lives have been saved by antibiotics since they were fi rst discovered
about 90 years ago. For the fi rst few decades antibiotics had remarkable success.
Encouraged by the remarkable success, in 1969 the then-US Surgeon General
William Stewart testifi ed before Congress that it was “time to close the book on
infectious disease.” Today, we know how premature that statement was. More than
four decades later, infectious disease still remains the leading cause of death world-
wide, and ranks among the top ten causes of death in the United States. The main
reason is that bacteria are becoming increasingly resistant to antibiotics. Mechanisms
by which bacteria develop resistance to antibiotics are also discussed here.
T his book has been written with the student in mind. The main focus is to explain
how antibiotics work in curing infectious diseases and how resistance develops to
the antibiotics. A background in Biochemistry is needed to understand the mecha-
nism of action of the antibiotics. However, any background information that is
needed is discussed in the book. So, it will not be necessary for the student to con-
sult any separate biochemistry textbook in order to understand the theory of antibi-
otics. However, the discussion of biochemistry in this book is not meant to be
complete. The only information presented is what is relevant to the understanding
of antibiotics.
There are many other important aspects of antibiotics that are studied by doctors,
pharmacists, and scientists but are beyond the scope of this book. Some of these
aspects are briefl y mentioned but will not be discussed in much detail.
D osage, formulation, bioavailability, and biostability are important aspects for
effective use of antibiotics. These ensure that the antibiotic will be delivered specifi -
cally to diseased site in the right amount and for the required duration. Dose depends
on how much of the antibiotic is absorbed from the digestive system, how stable it
is, how much enters the cells, the distribution of the drug in various tissues, and
many other factors. However, discussions of these aspects are beyond the scope of
this book.
vii
viii Preface
All antibiotics do not work for all infections. Antibiotics also have various side
effects and may interact with other drugs to give unwanted effects. Information
needed to decide which antibiotic to prescribe for which infection is beyond the
scope of this book.
A ll antibiotics will be referred to by their common names such as penicillin,
tetracycline, and erythromycin even though many of these antibiotics have other
brand names. There are also various derivatives with altered but similar activities
for many of these antibiotics. Not all of these names are included in this book. All
antibiotics will also have a systematic name based on IUPAC nomenclature of
organic compounds. Those names will be mentioned for the simple molecules but
not for those with complex structures.
Brooklyn, NY, USA Mrinal K. Bhattacharjee
Contents
1 Introduction to Antibiotics ....................................................................... 1
1.1 Defi nition of Antibiotics .................................................................... 1
1.2 History of Antibiotics ......................................................................... 3
1.3 The Ideal Antibiotic ........................................................................... 4
1.4 Sources of Antibiotics ........................................................................ 5
1.5 Discovery of Modern Antibiotics ....................................................... 6
1.6 Classifi cation of Antibiotics ............................................................... 10
1.7 Background Biochemistry Information ............................................. 12
1.7.1 Enzymes ................................................................................. 12
1.7.2 Enzyme Inhibitors .................................................................. 13
1.7.3 Enzyme Mechanisms ............................................................. 14
1.7.4 Metabolism and Metabolic Pathways .................................... 16
1.7.5 Thermodynamics of Metabolic Pathways .............................. 18
1.7.6 High Energy Compounds ....................................................... 19
1.7.7 Metabolically Irreversible and Near Equilibrium
Reactions ................................................................................ 22
1.7.8 Membrane Transport .............................................................. 24
2 Development of Resistance to Antibiotics ............................................... 27
2.1 Antibiotics Are No Longer Considered to be Miracle Drugs ............ 27
2.2 Detection of Antibiotic Resistance ..................................................... 28
2.3 Classifi cation of Antibiotic Resistance .............................................. 29
2.4 Resistance Development by Point Mutations .................................... 29
2.5 Selection for Resistance ..................................................................... 31
2.6 Resistance Development by Resistance Gene Acquisition ................ 32
2.7 Mechanism of Antimicrobial Resistance ........................................... 36
2.8 Synthetic Antibiotics .......................................................................... 36
2.9 Alternative Approaches for Studying Antibiotics .............................. 39
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