Chemistry of Antibiotics and Related Drugs

Preface
Contents
Chapter 1: Introduction to Antibiotics
1.1 Definition of Antibiotics
1.2 History of Antibiotics
1.3 The Ideal Antibiotic
1.4 Sources of Antibiotics
1.5 Discovery of Modern Antibiotics
1.6 Classification of Antibiotics
1.7 Background Biochemistry Information
1.7.1 Enzymes
1.7.2 Enzyme Inhibitors
1.7.3 Enzyme Mechanisms
1.7.4 Metabolism and Metabolic Pathways
1.7.5 Thermodynamics of Metabolic Pathways
1.7.6 High-Energy Compounds
1.7.7 Metabolically Irreversible and Near-Equilibrium Reactions
1.7.8 Membrane Transport
References
Chapter 2: Development of Resistance to Antibiotics
2.1 Antibiotics Are No Longer Considered to Be Miracle Drugs
2.2 Detection of Antibiotic Resistance
2.3 Classification of Antibiotic Resistance
2.4 Resistance Development by Point Mutations
2.5 Selection for Resistance
2.6 Resistance Development by Resistance Gene Acquisition
2.7 Mechanism of Antimicrobial Resistance
2.8 Synthetic Antibiotics
2.9 Alternative Approaches for Studying Antibiotics
2.10 Antibiotic Use in Animals
2.10.1 Therapeutic Use
2.10.2 Subtherapeutic Use
2.11 Prevention of Antibiotic Resistance Development
References
Chapter 3: Antibiotics That Inhibit Cell Wall Synthesis
3.1 Background Biochemistry Information
3.1.1 Carbohydrates
3.1.2 Molecular Structure of Bacterial Cell Wall
3.2 Biosynthesis of Peptidoglycan of the Cell Wall
3.2.1 Stage 1: The Cytosolic Phase of Synthesis
3.2.2 Stage 2: The Membrane Phase of Synthesis
3.2.3 Stage 3: The Cell Wall Phase of Synthesis
3.3 Antibiotics That Inhibit Cell Wall Biosynthesis
3.3.1 Antibiotics Targeting the Cytosolic Phase of Synthesis
3.3.1.1 Fosfomycin
3.3.1.2 D-Cycloserine
3.3.2 Antibiotics Targeting the Cell Wall Phase of Synthesis
3.3.2.1 Penicillin
3.3.2.2 Cephalosporin
3.3.2.3 Mechanism of Action of Penicillin
3.3.2.4 Resistance to β-Lactam Antibiotics
3.3.2.5 β-Lactamase: An Enzyme That Inactivates β-Lactam Drugs
3.3.2.6 Mechanism of Action of β-Lactamases
3.3.2.7 β-Lactamase Inhibitors
3.3.2.8 Inhibitors of Metallo-β-Lactamases
3.3.2.9 Extended-Spectrum β-Lactamases (ESBLs)
3.3.2.10 Methicillin-Resistant Staphylococcus aureus (MRSA)
3.3.2.11 Unusual β-Lactams: Monobactams
3.3.2.12 Unusual β-Lactams: Carbapenems
3.3.3 Antibiotics Targeting the Membrane Phase of Synthesis
3.3.3.1 Bacitracin
3.3.3.2 Antibiotics That Inhibit Transglycosylation Reaction
3.3.3.3 Moenomycin
3.3.3.4 Lantibiotics: Mersacidin
3.3.3.5 Vancomycin
3.3.3.6 Mechanism of Action of Vancomycin
3.3.3.7 Resistance Development to Vancomycin
3.3.4 Teixobactin, A Newly Discovered Antibiotic
References
Chapter 4: Antimetabolites: Antibiotics That Inhibit Nucleotide Synthesis
4.1 Antimetabolites
4.2 Background Biochemistry Information: Folic Acid
4.3 Antibiotics That Inhibit Folate Metabolism
4.3.1 Sulfa Drugs
4.3.2 Mechanism of Action of Sulfonamides
4.3.3 Negative Aspects of Sulfonamides
4.3.4 Non-sulfonamide Antimetabolites of Folic Acid
4.3.5 Antimetabolites as Dihydrofolate Reductase (DHFR) Inhibitors
4.3.6 Antimetabolites as Antibacterial, Antimalarial, and Anticancer Agents
4.3.6.1 Combination Antibiotics
4.3.7 Thymidylate Synthase Inhibitor: 5-Fluorouracil
4.3.8 Other Antimetabolites: Azaserine and Diazo-Oxo-Norleucine
References
Chapter 5: Antibiotics That Inhibit Nucleic Acid Synthesis
5.1 Background Biochemistry Information
5.1.1 Structure of Nucleotides
5.1.2 Watson-Crick Model of DNA
5.1.3 Superhelical Structure of DNA
5.1.4 DNA Replication
5.2 Intercalators as Antibiotics
5.3 Inhibitors of DNA Gyrase: Quinolones
5.3.1 Mechanism of Resistance to Quinolones
5.4 Nitroheterocyclic Aromatic Compounds as Antibiotics
5.4.1 Nitroimidazoles: Antibiotics That Cleave DNA
5.4.2 Nitrofurans: Multiple Possible Mechanisms of Action
5.5 RNA Synthesis: Background Biochemistry Information
5.6 Rifamycins
5.7 Actinomycin D (Dactinomycin)
5.8 Fidaxomicin: A New Antibiotic with a New Target
References
Chapter 6: Antibiotics That Inhibit Protein Synthesis
6.1 Protein Synthesis: Background Biochemistry Information
6.2 Antibiotics That Inhibit Protein Synthesis
6.2.1 Puromycin
6.2.2 Aminoglycosides
6.2.3 Resistance to Aminoglycosides
6.2.4 Tetracyclines
6.2.5 Chloramphenicol
6.2.6 The MLS Group of Antibiotics
6.2.6.1 Macrolides
6.2.6.2 Lincosamides
6.2.6.3 Streptogramins
6.2.7 Two Truly New Antibiotics
6.2.7.1 Oxazolidinones
6.2.7.2 Pleuromutilins
6.2.8 Protein Synthesis Antibiotics with Unusual Mechanisms of Action
6.2.8.1 Thermorubin
6.2.8.2 Fusidic Acid
6.2.8.3 Mupirocin
6.2.8.4 Peptide Deformylase Inhibitors: Actinonin
6.2.8.5 Methionine Aminopeptidase Inhibitors
References
Chapter 7: Antibiotics That Affect the Membrane and Other Structural Targets
7.1 Background Biochemistry Information
7.1.1 Function of Biological Membranes
7.1.2 Composition of the Membrane
7.2 Inhibition of Bacterial Membrane Function
7.2.1 Antiseptics and Disinfectants That Disrupt Microbial Cell Membrane
7.2.2 Antibiotics that Function by Disrupting Microbial Cell Membrane
7.2.2.1 Antimicrobial Peptides (AMPs)
7.2.2.2 Gramicidins
7.2.2.3 Tyrocidine
7.2.2.4 Gramicidin S
7.2.2.5 Polymyxins and Colistins
7.2.2.6 Daptomycin
7.2.2.7 Other AMPs: Defensins, Magainins, Bacteriocins
7.2.2.8 Lantibiotics
7.3 Antibiotics Affecting Other Structural Targets
7.3.1 Triclosan, The Antibiotic That Inhibits Fatty Acid Synthesis
7.3.2 Isoniazid: Antibiotic Against Tuberculosis
7.3.3 Antibiotics Targeting FtsZ, The Cell Division Protein
References
Chapter 8: Antifungals, Antimalarials, and Antivirals
8.1 Antifungal Drugs: Antibiotics That Inhibit Growth of Fungi
8.1.1 Antibiotics That Bind to Ergosterol: Polyenes
8.1.2 Antibiotics That Inhibit Biosynthesis of Ergosterol
8.1.2.1 Azoles
8.1.2.2 Allylamines and Morpholines
8.1.3 Antibiotics That Inhibit Biosynthesis of Fungal Cell Wall
8.1.4 Flucytosine: Antimetabolite Antibiotic That Inhibits Fungal DNA and Protein Syntheses
8.1.5 Combination Therapy Against Fungal Infection
8.2 Antimalarial Drugs: Antibiotics That Inhibit Growth of Malarial Parasites
8.2.1 DDT the Most Well-Known Insecticide
8.2.2 Antimalarial Drugs: Quinine, Chloroquine, and Mefloquine
8.2.3 Antifolates as Antimalarial Antibiotics
8.2.4 Artemisinins
8.2.5 Quick Detection of Resistant Strains
8.3 Antiviral Drugs: Agents That Inhibit Multiplication and Spread of Viruses
8.3.1 Targets of Antiviral Antibiotics
8.3.2 Antivirals That Inhibit Entry and Uncoating of Viruses
8.3.3 Antivirals That Inhibit Synthesis of DNA or RNA of Viruses
8.3.4 Protease Inhibitors as Antiviral Drugs
8.3.5 Neuraminidase Inhibitors as Antiviral Drugs
8.3.6 Antiviral Drugs with Unusual Mechanisms of Action
8.3.6.1 Antisense Oligonucleotides
8.3.6.2 Interferons
8.3.7 Resistance Development Against Antiviral Drugs
References
Chapter 9: Alternative Approaches for Antibiotic Discovery
9.1 Drug Repurposing
9.1.1 Repurposing the Anticancer Drug YM155
9.1.2 Chloroquine
9.1.3 Teicoplanin
9.1.4 Remdesivir
9.2 Anti-virulence Approaches
9.2.1 Inhibition of Quorum Sensing
9.2.2 Inhibition of Biofilms
9.2.3 Bacterial Toxin Neutralization
9.2.4 Metal Ion Chelation
9.3 New Sources of Antibiotics
9.3.1 New Appropriate Methods for Antibiotic Discovery
9.3.2 Antibiotics from Plants
9.3.3 Antibiotics Against Persisters and Slow-Growing Bacteria
9.3.4 Nanoparticles as Antibiotics
9.4 Improving Delivery of Antibiotics
9.4.1 Steps to Increase Antibiotic Bioavailability
9.4.2 Nanoparticles for Drug Delivery
9.4.3 Antibiotics Against Intracellular Pathogens
References
Chapter 10: Global Action Plan and Antibiotic Stewardship
10.1 Global Action Plan
10.2 National Action Plans
10.2.1 National Action Plan of USA
10.2.2 National Action Plans of the European Commission
10.2.3 National Action Plan of China
10.2.4 National Action Plan of India
10.3 Antibiotic Stewardship Programs
10.3.1 Definition
10.3.2 Significance of Antibiotic Stewardship
10.3.3 Regulatory Agencies
10.3.4 Healthcare Providers
10.3.5 Farmers Use Antibiotics for Growth Promotion of Animals
10.3.6 Patients Have a Great Responsibility
10.3.7 Uncontrolled and Unlicensed Drug Formulations
10.3.8 Government Can Bring About the Fastest Changes
10.3.8.1 Cost Factor
10.3.8.2 Research Funding
10.3.9 Researchers Make the Greatest Contribution Towards Antibiotic Discovery
10.3.10 Print and Online News Media Have a Role to Play
10.4 Antibiotic Use in Dentistry
10.4.1 Antibiotics for Prophylaxis
10.4.2 Antibiotics for Toothache
10.4.3 Antibiotics Following Tooth Extraction
10.5 Vaccines Against Bacteria
References
Index