Targeted Metallo-Drugs: Design, Development, and Modes of Action

Description

Volume 24, entitled Targeted Metallo-Drugs: Design, Development, and Modes of Action, of the series Metal Ions in Life Sciences (MILS), fosters inter-disciplinary research in the vibrant field of Biological Inorganic Chemistry. Inspired by the clinical success of cisplatin as a leading anticancer drug but mindful of the shortcomings associated with its use including dose-limiting toxic side effects and acquired or intrinsic drug resistance, scientists across the globe have been endeavoring to identify new metallo-drugs for therapeutic exploitation. This has led to innovative metallo-drug candidates that (i) enhance cancer cell selectivity, thus reducing toxic side effects, and/or (ii) possess new modes of action to improve efficacy and also target resistance pathways. This and more are captured in MILS- 24 which consists of 12 comprehensive, well-illustrated, and up to date chapters with over 1600 citations, 100 figures, and 10 tables with key contributions from 32 international experts from Europe, Asia, and North and South America. MILS- 24 not only keeps the scientific community abreast of latest developments, it also serves as an invaluable resource to stimulate further research on targeted metallo-drug design and development. It covers anticancer, antimicrobial, antiviral, and other agents, such as those targeting tropical diseases and cyanide poisoning and radiometals in molecular imaging and therapy It highlights recent metallo-drug developments targeting COVID-19. It features advanced spectroscopic methods and metallomics as important tools to elucidate the modes of actions of metallo-drugs Cover Metal Ions in Life Sciences: Volume 24 Targeted Metallo-Drugs: Design, Development, and Modes of Action Copyright About the Editors Historial Development and Perspectives of the Series Preface to Volume 24 Contents Contributors to Volume 24 Handbooks and Book Series Published and (Co-)Edited by the SIGELs 1. Metal-Based Prodrugs Activated by Cancer-Specific Stimuli 1. Introduction 1.1 Anticancer Metal Complexes: Clinical Situation 1.2 Intrinsic Parameters of the Malignant Tumor Suitable for Drug Activation 1.2.1 Activation by Reduction Based on the Changed Redox Environment of the Tumor 1.2.2 Physicochemical Triggers: Hypoxia and Reduced pH 1.2.3 Biological Characteristics: Tumor-Specific Upregulation of Enzymes 2. Redox-Responsive Metal-Based Prodrugs 2.1 Redox-Responsive Pt Complexes 2.2 Nanomaterials Releasing Redox-Responsive Pt Drugs 2.3 Redox-Responsive Ru Complexes 2.4 Redox-Responsive Nanomaterials of Ru Compounds 2.5 Redox-Responsive Cu Complexes and Their Nanoformulations 3. Hypoxia-Responsive Metal-Based Prodrugs 3.1 Hypoxia-Responsive Co Complexes 3.2 Hypoxia-Responsive Cu, Fe, and Au Complexes 3.3 Hypoxia-Responsive Nanosystems Releasing Metal Drugs 4. pH-Responsive Metal-Based Prodrugs 4.1 pH-Responsive Pt Complexes 4.2 pH-Responsive Pt Nanomaterials 4.3 pH-Responsive Ru Drugs and Nanomaterials 5. Enzyme-Activatable Metal-Based Drugs and Nanomaterials 5.1 Enzyme-Activatable Prodrugs 5.2 Enzyme-Activatable Nanomaterials Releasing Metal Drugs 6. General Conclusion Acknowledgments Abbreviations References 2. Light-Activated Drugs for Photodynamic and Photoactivated Therapy 1. Introduction 1.1 A Short History of Photosensitizers and Photoactivators 1.2 Mechanisms of Photophysical and Photochemical Action 1.3 Recent Progress in Metal-Based Light-Activated Drug Discovery 1.4 Highlights of Successful Drugs for Photodynamic Therapy 1.5 Ongoing Challenges and Missed Opportunities 2. Traditional Medicinal Chemistry Guidelines 3. Proposed Guidelines for Light-Activated Systems 4. Example Systems Based on Different Mechanism of Action 4.1 Organic vs. Metal Containing Photosensitizers 4.1.1 Photocatalysts That Generate [sup(1)]O[sub(2)] 4.1.2 Other Types of Photocatalysts 4.2 Organic vs. Metal Containing Photoactivated Agents 4.2.1 Organic Photocages 4.2.2 Inorganic Photocages 4.2.3 Organic Photocages Activated by [sup(1)]O[sub(2)] 4.2.4 Organic Photoswitches 4.2.5 Inorganic Photoswitches 4.2.6 Cofactor Mimics for Prodrug Activation 4.2.7 Exploiting Endogenous Biosynthetic Pathways: Protoporphyrin IX Formation 4.2.8 Gasotransmitter Release From Inorganic Molecules 4.2.9 Nanomedicine 4.2.10 Covalent Biomolecule Modification 5. General Conclusions Acknowledgments Abbreviations and Definitions References 3. Mitochondria as a Metallo-Drug Target for Therapeutic Purposes 1. Introduction 1.1 Mitochondria as Unusual Cell Organelles 1.2 Role of the Mitochondria in Cell Death Pathways 1.2.1 Apoptosis 1.2.2 Non-Apoptotic Cell Death 1.3 Mitochondrial Diseases 1.4 Mitochondria and Cancer 2. Mitochondria as Drug Targets 3. Mechanistic Studies of Mitochondria-Targeting Metallo-Drugs 4. Accumulation of Metallo-Drugs in the Mitochondria 5. Mitochondria-Targeting Metal-Based Cancer Drugs 5.1 Platinum Complexes 5.2 Gold Complexes 5.3 Ruthenium, Iridium, and Rhenium Complexes 5.4 Copper Complexes 5.5 Photoactivated Metallo-Drugs and Metal-Based Photosensitizers 6. Concluding Remarks and Perspectives Acknowledgments Abbreviations References 4. Transition Metal-Based Antiviral Agents Against SARS-CoV-2 and Other Pathogenic Viruses 1. Introduction 2. Background on Metal-Based Antiviral Agents 2.1 Pathogenic Viruses with Relevance for Metal-Based Antiviral Agents 2.2 Antiviral Drug Targets of Relevance for Metal-Based Compounds 3. Period 4 Metal-Based Antiviral Agents 3.1 Scandium to Iron in Antiviral Metal Complexes 3.2 Cobalt Complexes as Antiviral Agents 3.3 Nickel Complexes as Antiviral Agents 3.4 Copper Complexes as Antiviral Agents 3.5 Zinc Complexes as Antiviral Agents 3.5.1 Zinc Complexes Against Different Viruses 3.5.2 Antiviral Properties of Zinc Against Respiratory Viruses 4. Period 5 Metal-Based Antiviral Agents 4.1 Yttrium to Technetium in Antiviral Metal Complexes 4.2 Ruthenium, Rhodium and Palladium Complexes as Antiviral Agents 4.3 Silver and Cadmium Complexes as Antiviral Agents 5. Period 6 and 7 Metal-Based Antiviral Agents 5.1 Lanthanum to Platinum in Antiviral Metal Complexes 5.2 Gold Complexes as Antiviral Agents 5.2.1 Gold Complexes Against HIV and Other Viruses 5.2.2 Gold Complexes as SARS-CoV-2 Antivirals 5.3 Mercury Complexes as Antiviral Agents 6. Summary and Outlook Acknowledgements Abbreviations References 5. Exploiting the Chemical Diversity of Metal Compounds as a Source of Novel Anti-COVID-19 Drugs 1. Metal Substances as a Rich Source of Drugs 2. The COVID-19 Disease: Some General Remarks 3. Metal Compounds as Potential Anti-COVID-19 Agents: A Few Remarkable Examples 3.1 Auranofin 3.2 Silver Sulfadiazine 3.3 [Co(Acacen)(NH[sub(3)])[sub(2)]]Cl 3.4 Bismuth Compounds 4. Toward a More Systematic Approach in the Search for Metal-Based Drugs for COVID-19 Disease 4.1 Selection of Metallo-Drugs for the Screening 4.2 Assessment of Metal Compounds as Inhibitors of the Interaction Between the S Protein and the ACE2 Receptor 4.3 Assessment of Metal Compounds as Inhibitors of the Papain-Like Protease 4.4 Assessment of Metal Compounds as Anti-SARS-Cov-2 Agents 5. Conclusions Acknowledgements Abbreviations References 6. Evaluating the Potential of Novel Metal-Based Drugs for Treating Drug-Resistant Bacteria 1. Introduction 1.1 Overview of Conventional Antibiotics 2. MRSA: An Antibiotic-Resistant Pathogen with a Significant Clinical Burden 2.1 Treatment 3. Metal-Based Drugs as Antibacterial Agents 3.1 Copper 3.1.1 Copper Antibacterial Mode of Action 3.1.2 Copper-Based Antibacterial Compounds 3.1.3 Safety and Toxicology of Copper-Based Antibacterial Compounds 3.2 Silver 3.2.1 Silver Antibacterial Mode of Action 3.2.2 Silver-Based Antibacterial Compounds 3.2.3 Safety and Toxicology of Silver-Based Antibacterial Compounds 3.3 Gold 3.3.1 Gold Antibacterial Mode of Action 3.3.2 Gold-Based Antibacterial Compounds 3.3.3 Safety and Toxicology of Gold-Based Antibacterial Compounds 3.4 Gallium 3.4.1 Gallium Antibacterial Mode of Action 3.4.2 Gallium-Based Antibacterial Compounds 3.4.3 Safety and Toxicology of Gallium-Based Antibacterial Drugs 3.5 Tellurium 3.5.1 Tellurium Antibacterial Mode of Action 3.5.2 Tellurium-Based Antibacterial Compounds 3.5.3 Safety and Toxicology of Tellurium-Based Antibacterial Compounds 3.6 Zinc Chelators 3.6.1 Zinc Chelators Combined with β-Lactams Antibacterial Mode of Action 3.6.2 Zinc Chelator-Based Antibacterial Compounds 3.6.3 Safety and Toxicology of Zinc Chelators Combined with β-Lactams 4. General Conclusion Abbreviations References 7. Prospective Metallo-Drugs Including Bioactive Compounds: Selection of Co-Ligands to Tune Biological Activity Against Neglected Tropical Diseases 1. Introduction 1.1 Neglected Tropical Diseases 2. Rational Design of Prospective Metallo-Drugs 3. Selection of Co-Ligands 3.1 Non-Active Co-Ligands: Improving Relevant Physicochemical Properties 3.2 Bioactive Co-Ligands: Development of Multifunctional Compounds 4. General Conclusions Acknowledgments Abbreviations and Definitions References 8. Challenges in Targeting Cyanide Poisoning: Advantages in Exploiting Metal Complexes in its Treatment 1. Introduction 2. Cyanide Concentrations In Vivo 2.1 Tissue Uptake and Distribution of Cyanide 2.2 Treatment of Cyanide Toxicity with Organic Compounds 3. Metal Antidotes 3.1 Methemoglobin 3.2 Cobalt Compounds and Toxicity 3.3 Cobalt Compounds in Clinical Use 3.4 Emerging Cobalt Compounds 3.5 Molybdenum Compounds 4. Advantages of Metalloantidotes 5. Concluding Remarks Abbreviations and Definitions References 9. Advanced Microscopy Methods for Elucidating the Localization of Metal Complexes in Cancer Cells 1. Introduction 2. X-Ray Fluorescence Microscopy 2.1 Fundamentals of X-Ray Fluorescence Imaging 2.2 Selected Biomedical Problems Investigated by X-Ray Fluorescence Microscopy of Metal Complexes 3. Luminescence Lifetime Imaging Microscopy 3.1 Advantages of Luminescence Lifetime Microscopy Over Confocal Microscopy 3.2 Selected Biomedical Problems Investigated by Luminescence Lifetime Microscopy of Metal Complexes 3.2.1 Detection of the Metal Complexes Through Elimination of Background Fluorescence 3.2.2 Detection of the Change in Localization of Metal Complexes by Changes in their Lifetime in Different Cellular Environments 3.2.3 Metal Complexes as Luminescent Lifetime Sensors 3.2.4 Conversion of Metal Complexes Inside Cancer Cells 4. Two-Photon Excitation Microscopy 4.1 Advantages of Two-Photon Excitation Over One-Photon Excitation 4.2 Advantages of Metal Complexes as Two-Photon Excited Chromophores 4.3 Selected Biomedical Problems Investigated by Two-Photon Excitation Microscopy of Metal Complexes 4.3.1 Metal Complexes as Two-Photon Excited Cell Organelle Dyes 4.3.2 Metal Complexes as Two-Photon Excited Sensors for Small Molecules 4.3.3 Metal Complexes as Two-Photon Excited Luminophores for Biomolecules 5. Conclusions Acknowledgments Abbreviations References 10. Metalloproteomics: A Powerful Technique for Metals in Medicine 1. Introduction 2. Methodology of Metallomics and Metalloproteomics 2.1 Mass Spectrometry: Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) and Mass Cytometry 2.2 Photoaffinity Chemical Probes for Mining Metalloproteins 2.3 Nuclear-Based Techniques 2.4 Immobilized Metal Affinity Chromatography (IMAC) 2.5 Integration of Metalloproteomics with Other-Omics and Deep Learning 3. Implementation on Biomedical Studies 3.1 Anticancer Drugs 3.2 Antimicrobial Drugs 4. Conclusion and Outlook Acknowledgments Abbreviations References 11. Metal-Based Nanoclusters for Biomedical Applications 1. Introduction 2. Characterization of Nanoclusters 2.1 Metal Nanoclusters: Basic Concepts and Preparation Possibilities 2.2 Structural Characteristics 2.3 Optical Characteristics 3. Biomedical Applications of Noble Metal Nanoclusters 3.1 Detection and Other Sensor Possibilities 3.1.1 Detection of Metal Ions and Inorganic Anions 3.1.2 Detection of Small Molecules 3.1.3 Detection of Proteins and Nucleic Acids 3.2 Bioimaging and Biolabeling 3.3 Drug Delivery 3.4 Diagnostics and Therapy 4. General Conclusions Acknowledgments Abbreviations and Definitions References 12. Radiometals in Molecular Imaging and Therapy 1. Introduction 2. Properties of Radiometals 2.1 The Types of Radioactive Decays 2.2 Choice of Radiometal for Medical Application 3. Production Methods of Radiometals 3.1 Nuclear Reactors 3.2 Accelerators 3.3 Radionuclide Generators 3.4 Impact of Production Method on the Suitability of Radiometals for Medical Applications 4. Characteristics of Selected Radiometals Used in Radiopharmaceuticals 4.1 Technetium-99m, Rhenium-186 and Rhenium-188 4.2 Indium-111 4.3 Gallium-68 4.4 Copper-61, Copper-64, and Copper-67 4.5 Scandium-43, Scandium-44, and Scandium-47 4.6 Zirconium-89 4.7 Yttrium-86 and Yttrium-90 4.8 Lutetium-177 4.9 Alpha-Emitting Radiometals 5. Chelators for Metal Complexation 6. Current Trends in Radiometals for Medical Application 7. General Conclusions Acknowledgement Abbreviations and Definitions References Index