دانلود کتاب Biomedical Chemistry: Current Trends and Developments

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Cover
Half Title
Biomedical Chemistry: Current Trends and Developments
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Contents
Preface
Section 1: Chemical Principles in Drug Design and Discovery
1.1. Functional Groups of Biomolecules and their Reactions
1.1.1 Functional Groups in Biological Systems
1.1.2 Acids and Bases Versus Electrophiles and Nucleophiles
1.1.3 Stereoisomerism and Chirality
1.1.3.1 Cis/trans Isomerism
1.1.3.2 Chirality and Enantiomerism
1.1.4 Common Mechanisms in Biological Chemistry
1.1.4.1 Nucleophilic Substitution Reactions
1.1.4.1.1 SN2 - Bimolecular Nucleophilic Substitution
1.1.4.1.2 SN1 ‒ Unimolecular Nucleophilic Substitution Reactions
1.1.4.1.3 Phosphate Group Transfer - the Grey Area of Nucleophilic Substitutions in Biological Syste
1.1.4.2 Electrophilic Addition Reactions
1.1.4.2.1 Synthesis of α-Terpineol ‒ Intramolecular Addition
1.1.4.3 Aromatic Substitutions
1.1.4.3.1 Electrophilic Aromatic Substitution
1.1.4.3.2 Nucleophilic Aromatic Substitutions
1.1.4.3.3 Hallucinogen Synthesis ‒ Aromatic Substitution on Fungi
1.1.4.4 Eliminations Reactions
1.1.4.4.1 E1 ‒ Unimolecular Elimination
1.1.4.4.2 E2 ‒ Bimolecular Elimination
1.1.4.4.3 E1cB ‒ Unimolecular Elimination through Conjugate Base
1.1.4.5 Nucleophilic Carbonyl Addition Reactions
1.1.4.5.1 Nitrofurantoin ‒ a Semicarbazone
1.1.4.6 Acyl Substitution Reactions
1.1.4.6.1 Aspirin ‒ Esterifications and Transesterifications
1.1.4.7 Carbonyl Condensation Reactions
1.1.4.7.1 Aldol Reaction
1.1.4.7.2 Claisen Condensation
1.1.4.7.3 Aldolases ‒ Stabilization Strategies
1.1.4.8 Oxidations and Reductions
1.1.4.8.1 Disulfide Bridges ‒ Oxidized Thiols
1.1.5 The Organic Mechanisms of Biological Transformations
1.1.5.1 Cis/trans-Isomers Interconversion in the Vision Pathway
1.1.5.2 Metabolism of Fatty Acids ‒ β-Oxidation Pathway
1.1.5.3 Penicillin ‒ a Strong Acylating Agent
1.1.5.3.1 Transpeptidase Mechanism
1.1.5.3.2 Transpeptidase Inhibition
1.1.5.3.3. Penicillin Biosynthesis
1.1.5.4 NAD+ − a Classical Coenzyme
1.1.5.5. FAD − a More Versatile Coenzyme
1.1.5.6 Biotin and Carboxylation Reactions
References
1.2. Designing Covalent Inhibitors: A Medicinal Chemistry Challenge
1.2.1 Introduction
1.2.2 Designing Safer Covalent Inhibitors
1.2.3 Case Study 1: Michael Acceptors to Treat Infectious Diseases
1.2.3.1 K777 Inhibitor
1.2.3.2 Rupintrivir (AG7088)
1.2.4 Case Study 2: From Covalent Inhibitors to Hybrid Drugs
1.2.4.1 Hybrid Compounds Containing an Electrophilic Warhead
1.2.4.2 Hybrid Compounds Containing a Masked Electrophilic Warhead
1.2.5 Conclusions
References
Section 2: Chemical Basis of Drug Action and Diseases
2.1. Pharmacokinetics and Bioanalysis to Improve Drug Development
Abbreviations
2.1.1 Introduction
2.1.2 Pharmacokinetics on Drug Discovery and Development Process
2.1.2.1 ADME/Pharmacokinetic Evaluation on Early Drug Discovery Phases
2.1.2.2 Pharmacokinetic Evaluation on Drug Development Phases
2.1.3 Bioanalysis and Validation Requirements on DDD
2.1.4 Bioanalysis & Pharmacokinetics, a Synergistic Partnership on DDD
2.1.4.1 Bioanalytic Support of In Vitro ADME Studies
2.1.4.2 Bioanalytic Support of In Vivo ADME/Pharmacokinetic Studies
2.1.5 Conclusions
References
2.2. Translational Research in Endocrinology and Neuroimmunology Applied to Depression
2.2.1 Major Depressive Disorder
2.2.2 The Stress Response
2.2.2.1 The CRH System and the Stress Response
2.2.2.2 The Locus Ceruleus Norepinephrine (LC-NE) System and Other Central Nervous System (CNS) Stru
2.2.2.3 The Immune System
2.2.3 The Effect of Chronic Stress and MDD in Dysregulating the Core Stress System
2.2.4 Summary and Conclusions
References
2.3. Understanding the Metabolic Syndrome Using a Biomedical Chemistry Profile
2.3.1 Introduction
2.3.2 Natural Mineral-rich Waters and MetSyn
2.3.3 Magnesium and MetSyn/MetSyn Features - Associated Mechanisms
2.3.4 Calcium and MetSyn/MetSyn Features - Associated Mechanisms
2.3.5 Potassium and MetSyn/MetSyn Features - Associated Mechanisms
2.3.6 Bicarbonate and MetSyn/MetSyn Features - Associated Mechanisms
2.3.7 Magnesium, Calcium, Potassium and Bicarbonate versus Sodium
2.3.8 Conclusion
References
2.4. Brain Neurochemistry and Cognitive Performance: Neurotransmitter Systems
2.4.1 Monoaminergic Neurotransmission and Cognition
2.4.2 Glutamate Neurotransmission and Cognition
2.4.3 GABAergic Neurotransmission and Cognition
2.4.4 Gliotransmitters
2.4.5 Cognitive Enhancement
References
Section 3: Strategies to Develop New and Better Drugs
3.1. Amino Acids and Peptides in Medicine: Old or New Drugs?
3.1.1 Introduction
3.1.1.1 Amino acids: biological and chemical concepts
3.1.2 Amino Acids and Drug Development
3.1.2.1 Rationale for Drug Design
3.1.2.2 Amino Acid Prodrug in Drug Delivery
3.1.2.3. L-type Amino Acid Transporter
3.1.2.4. Variability of Amino Acid Application to Exclusive Drugs
3.1.3 Peptides for Biomedicine
3.1.3.1 Antimicrobial Peptides (AMPs)
3.1.3.1.1 AMPs: Mechanism of Action and Peptide Families
3.1.3.1.2 α-Helical Peptides without Cys Residues
3.1.3.1.3 Peptides Containing Disulfide Bridges
3.1.3.1.4 Peptides Rich in Pro, Gly, His, Arg and Trp Residues
3.1.3.3 Peptides: Scaffolding Materials in Tissue Engineering
3.1.3.3.1 Peptide-based Biopolymers
3.1.3.3.2 Strategies to Create Scaffolds as Instructive Extracellular Microenvironments for Tissue E
3.1.3.3.3 Peptide-based Biomaterials Responsive to Environmental Cues
3.1.3.3.4 Self-assembling Peptides as Biomaterials
3.1.3.4 Therapeutic Peptides and Market
3.1.3.4.1 Chemical Strategies to Improve Peptide Biological Activity
3.1.3.4.2 Market
3.1.4 Conclusions
References
3.2. Targeting Calcium-mediated Excitotoxicity in the CNS
3.2.1 Introduction
3.2.2 Glutamate and Glutamate Receptors
3.2.2.1 AMPA Receptors
3.2.2.2 Kainate Receptors
3.2.2.3 NMDA Receptors
3.2.3 The Role of Calcium in Normal Neuronal Biochemistry
3.2.4 Excitotoxicity
3.2.5 The Role of Calcium in Excitotoxic Neuronal Biochemistry
3.2.6 Diseases that are Potentially Exacerbated by Calcium-mediated Excitotoxicity
3.2.6.1 Amyotrophic Lateral Sclerosis (ALS)
3.2.6.2 Multiple Sclerosis (MS)
3.2.6.3 Alzheimer’s Disease (AD)
3.2.6.4 Huntington’s Disease (HD)
3.2.6.5 Stroke
3.2.6.6 Parkinson’s Disease
3.2.6.7 Traumatic Brain or Spinal Cord Injury
3.2.7 Why not Fully Block Calcium Entry via Pharmacological Agents?
3.2.8 Emerging Targets for Reducing Calcium-mediated Excitotoxicity
3.2.9 Conclusions and Outlook
References
3.3. Strategies for Conversion of Peptides to Peptidomimetic Drugs
3.3.1 Peptides as Starting Points in Drug Discovery
3.3.1.1 Strategy for the Development of Peptidomimetics
3.3.1.1.1 Property Elucidation
3.3.1.1.2 Structure-Activity Relationship
3.3.1.1.3 Bioactive Conformation
3.3.1.1.3.1 Secondary Structure Mimetics
3.3.2 A Case study of Rational Peptide Lead Optimization: Development of Small and Constrained Pepti
3.3.2.1 SP1-7 and its Binding Site
3.3.2.2 SAR and Truncation Studies of SP1-7 and EM-2
3.3.2.2.1 Strategy
3.3.2.2.2 Structure-activity Relationship
3.3.2.2.3 Effects of SP1-7 and its Analogs
3.3.2.3 Design and Synthesis of Small Constrained H-Phe-Phe-NH2 Analogs
3.3.2.3.1 Strategy
3.3.2.3.2 Structure-activity relationship and ADME properties
3.3.3 Conclusion
References
3.4. Synthetic Vs. Natural Bioactive Compounds Against Tropical Disease
3.4.1 Introduction
3.4.2 Early History of Malaria Treatment; Quinine and Artemisinin
3.4.3 Post World War II and the Development of Synthetic Anti-malarials
3.4.4 Modern Efforts in Antimalarial Drug Development
3.4.4.1 Quinine, 4-Aminoquinolines, and Quinoline Methanols
3.4.4.2 8-Aminoquinolines
3.4.4.3 Artemisinins and other Endoperoxides
3.4.4.4 Repurposed Drugs
3.4.5 Natural Products in the Treatment of Malaria
3.4.6 Considerations for Anti-parasitic Drug Development
References
3.5. Current Trends and Developments for Nanotechnology in Cancer
3.5.1 Introduction
3.5.2 Drug Delivery Nanosystems in Cancer Therapy
3.5.2.1 Controlled Drug Delivery
3.5.2.2 Stimuli-responsive Controlled Drug Delivery Systems
3.5.2.3 Combination Therapy
3.5.3 Cancer Targeting
3.5.3.1 Passive Targeting
3.5.3.1.1 The Fundamentals of Passive Targeting and the EPR Effect
3.5.3.1.2 Physicochemical Properties of Nanoparticles Affecting the Passive Targeting
3.5.3.1.3 Challenges and Future Prospects of Passive Targeting
3.5.3.2 Active Targeting
3.5.3.2.1 The Fundamentals of Active Targeting
3.5.3.2.2 Factors Affecting Tumor Active Targeting
3.5.3.2.3 Ligands for Tumor Active Targeting
3.5.3.2.3.1 Monoclonal Antibodies
3.5.3.2.3.2 Proteins and Peptides
3.5.3.2.3.3 Aptamers
3.5.3.2.3.4 Small Molecules
3.5.4 Nanotechnology and Immunotherapy
3.5.4.1 Nano-based Cancer Immunotherapy
3.5.4.2 Nanoparticulate Adjuvants for Cancer Immunotherapy
3.5.4.3 Nanoparticle Based DC Targeting for Cancer Immunotherapy
3.5.5 Cancer Imaging, Diagnostics and Multifuctional Nanosystems
3.5.6 Conclusions and Future Prospects
References
Index