Bioinorganic Medicinal Chemistry

This book gives a comprehensive overview about medicinal inorganic chemistry. Topics like targeting strategies, mechanism of action, Pt-based antitumor drugs, radiopharmaceuticals are covered in detail and offer the reader an in-depth overview about this important topic.

Enzo Alessio was born in 1958, studied chemistry at the University of Trieste (Italy) and received his Ph D from the University of Ferrara (Italy) in 1989. After a NATO-CNR postdoctoral fellowship with Luigi G. Marzilli at Emory University (Atlanta), he became first Research Associate and then Associate Professor of Inorganic Chemistry at the University of Trieste, where he is now director of the PhD School in Chemistry. He is co-author of more than 150 publications and 10 patents in the fields of coordination chemistry, metal-based anticancer drugs, and metal-driven construction of supramolecular architectures, in particular multi-chromophore assemblies for photophysical applications.

List of Contributors.

1 Medicinal Inorganic Chemistry: State of the Art, New Trends, and a Vision of the Future (Nicola J. Farrer and Peter J. Sadler).

1.1 Introduction.

1.2 Antimicrobial Agents.

1.3 Antiviral Agents.

1.4 Systemic and Metabolic Diseases Including Inflammation.

1.5 Metal Chelating Agents.

1.6 Antiarthritic Drugs and Inflammation.

1.7 Bipolar Disorder.

1.8 Anticancer Agents.

1.9 Small Molecule Delivery and Control.

1.10 Diagnostic Agents.

1.11 Veterinary Medicinal Inorganic Chemistry.

1.12 Conclusions and Vision.

2 Targeting Strategies for Metal-Based Therapeutics (Julia F. Norman and Trevor W. Hambley).

2.1 Introduction.

2.2 Physiological Targeting.

2.3 Molecular Targeting.

2.4 Immunological Targeting.

2.5 Concluding Remarks.

3 Current Status and Mechanism of Action of Platinum-Based Anticancer Drugs (Shanta Dhar and Stephen J. Lippard).

3.1 Introduction.

3.2 Mechanism of Action of Cisplatin.

3.3 Limitations of Current Platinum-Based Compounds: New Strategies.

3.4 Novel Concepts in the Development of Platinum Antitumor Drugs.

3.5 Concluding Remarks.

4 New Trends and Future Developments of Platinum-Based Antitumor Drugs (Xiaoyong Wang and Zijian Guo).

4.1 Introduction.

4.2 Mechanisms of Action and Resistance.

4.3 Monofunctional Platinum(II) Complexes.

4.4 Trans-Platinum(II) Complexes.

4.5 Multinuclear Platinum(II) Complexes.

4.6 Platinum(IV) Complexes.

4.7 Delivery of Platinum Drugs.

4.8 Concluding Remarks and Future Perspectives.

5 Ruthenium and Other Non-platinum Anticancer Compounds (Ioannis Bratsos, Teresa Gianferrara, Enzo Alessio, Christian G. Hartinger, Michael A. Jakupec, and Bernhard K. Keppler).

5.1 Introduction.

5.2 Ruthenium Anticancer Compounds.

5.3 From Gallium Nitrate to Oral Gallium Complexes.

5.4 Titanium Anticancer Compounds.

5.5 Ferrocene-Derived Anticancer Agents.

5.6 The Main Group Organometallics Spirogermanium and Germanium-132.

5.7 Arsenic in Cancer Chemotherapy.

5.8 Overcoming the Resistance of Tumors to Anticancer Agents by Rare Earth Element Compounds.

5.9 Conclusions.

6 The Challenge of Establishing Reliable Screening Tests for Selecting Anticancer Metal Compounds (Angela Boccarelli, Alessandra Pannunzio, and Mauro Coluccia).

6.1 Introduction.

6.2 Tumor Cell Growth Inhibition and Cell Death Screening Assays.

6.3 Metal-Based Anticancer Compounds and Gene Expression Microarray Technologies.

6.4 Metal-Based Anticancer Compounds and the Proteomic Approach.

6.5 Concluding Remarks.

7 Gold-Based Therapeutic Agents: A New Perspective (Susan J. Berners-Price).

7.1 Introduction.

7.2 Biological Chemistry of Gold.

7.3 Gold Antiarthritic Drugs.

7.4 Gold Complexes as Anticancer Agents.

7.5 Gold Complexes as Antiparasitic Agents.

7.6 Concluding Remarks.

8 MRI Contrast Agents: State of the Art and New Trends (Daniela Delli Castelli, Eliana Gianolio, and Silvio Aime).

8.1 Introduction.

8.2 T₁ Agents.

8.3 T₂-Susceptibility Agents.

8.4 CEST Agents.

8.5 Concluding Remarks.

9 Metal-Based Radiopharmaceuticals (Roger Alberto).

9.1 Introduction.

9.2 Selected Examples: Therapeutic Radiopharmaceuticals.

9.3 Diagnostic Metal-Based Radiopharmaceuticals.

9.4 Perspectives and Conclusion.

10 Boron and Gadolinium in the Neutron Capture Therapy of Cancer (Ellen L. Crossley, H. Y. Vincent Ching, Joseph A. Ioppolo, and Louis M. Rendina).

10.1 Introduction.

10.2 Boron Neutron Capture Therapy.

10.3 Role of Medicinal Inorganic Chemistry in BNCT.

10.4 Gadolinium Neutron Capture Therapy.

10.5 Conclusions and Future Outlook.

11 Essential Metal Related Metabolic Disorders (Yasmin Mawani and Chris Orvig).

11.1 Introduction: What is Essentiality?

11.2 Iron Metabolic Diseases: Acquired and Genetic.

11.3 Copper Metabolic Diseases.

11.4 Zinc Metabolic Diseases.

11.5 Diseases Related to Imbalances in Electrolytic Metabolism: P, the Alkali Metals, and the Alkaline Earths.

11.6 Metabolism of Other Trace Elements.

11.7 Conclusions.

12 Metal Compounds as Enzyme Inhibitors (Gilles Gasser and Nils Metzler-Nolte).

12.1 Introduction.

12.2 Kinase Inhibitors.

12.3 Proteasome Inhibitors.

12.4 Carbonic Anhydrase Inhibitors (CAIs).

12.5 Cyclooxygenase Inhibitors.

12.6 Acetylcholinesterase Inhibitors.

12.7 Protein Phosphatase Inhibitors.

12.8 Trypsin and Thrombin Inhibitors.

12.9 Cysteine Protease Inhibitors and Glutathione Transferase Inhibitors.

12.10 HIV-1 Reverse Transcriptase and Protease Inhibitors.

12.11 Telomerase Inhibitors.

12.12 Zinc Finger Protein Inhibitors.

12.13 CXCR4 Inhibitors.

12.14 Xanthine Oxidase Inhibitors.

12.15 Miscellaneous Protein Inhibitors and Conclusions.

13 Biomedical Applications of Metal-Containing Luminophores (Albert Ruggi, David N. Reinhoudt, and Aldrik H. Velders).

13.1 Introduction: Luminescence in Diagnostics and Imaging.

13.2 Transition-Metal Containing Luminescent Agents.

13.3 Lanthanide-Based Luminophores.

13.4 Nanoparticle-Based Luminophores.

13.5 Conclusions and Perspectives.

Index.