13. METAL COMPOUNDS IN THE DEVELOPMENT OF ANTIPARASITIC AGENTS: RATIONAL DESIGN FROM BASIC CHEMISTRY TO THE CLINIC
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Dinorah Gambino
Abstract
Metal compounds seem to be a promising approach in the search of new therapeutic solutions for neglected tropical diseases. In this chapter, efforts in the design of prospective metal-based drugs for the treatment of Chagas disease, human African trypanosomiasis, and leishmaniasis are discussed. Careful selection of the metal center (including organometallic cores) and the types and number of coordinated ligands is essential for controlling the reactivity of the complexes and hence, tuning their biological properties. In a target-based approach, some targets that have been validated for organic antiparasitic compounds are expected to remain targets for metal complexes of these compounds. In addition, specific targets for metal compounds, like parasitic enzymes or DNA, would also be included for these metal complexes leading to potential additive or even synergistic effects between organic ligand and metal ion. However, even though a good number of prospective antiparasitic metal-based drugs have been developed, further systematic efforts are needed for these metal compounds to accomplish the regulatory guidelines that let them reach the different stages of clinical trials.
Abstract
Metal compounds seem to be a promising approach in the search of new therapeutic solutions for neglected tropical diseases. In this chapter, efforts in the design of prospective metal-based drugs for the treatment of Chagas disease, human African trypanosomiasis, and leishmaniasis are discussed. Careful selection of the metal center (including organometallic cores) and the types and number of coordinated ligands is essential for controlling the reactivity of the complexes and hence, tuning their biological properties. In a target-based approach, some targets that have been validated for organic antiparasitic compounds are expected to remain targets for metal complexes of these compounds. In addition, specific targets for metal compounds, like parasitic enzymes or DNA, would also be included for these metal complexes leading to potential additive or even synergistic effects between organic ligand and metal ion. However, even though a good number of prospective antiparasitic metal-based drugs have been developed, further systematic efforts are needed for these metal compounds to accomplish the regulatory guidelines that let them reach the different stages of clinical trials.
Chapters in this book
- Frontmatter i
- About the Editors v
- Historical Development and Perspectives of the Series vii
- Preface to Volume 19 ix
- Contents xiii
- Contributors to Volume 19 xix
- Titles of Volumes 1–44 in the Metal Ions in Biological Systems Series xxiii
- Contents of Volumes in the Metal Ions in Life Sciences Series xxv
- 1. METALS IN MEDICINE: THE THERAPEUTIC USE OF METAL IONS IN THE CLINIC 1
- 2. SMALL MOLECULES: THE PAST OR THE FUTURE IN DRUG INNOVATION? 17
- 3. IRON CHELATION FOR IRON OVERLOAD IN THALASSEMIA 49
- 4. IRONING OUT THE BRAIN 87
- 5. INFECTIONS ASSOCIATED WITH IRON ADMINISTRATION 123
- 6. IRON OXIDE NANOPARTICLE FORMULATIONS FOR SUPPLEMENTATION 157
- 7. BUILDING A TROJAN HORSE: SIDEROPHORE-DRUG CONJUGATES FOR THE TREATMENT OF INFECTIOUS DISEASES 181
- 8. DEVELOPING VANADIUM AS AN ANTIDIABETIC OR ANTICANCER DRUG: A CLINICAL AND HISTORICAL PERSPECTIVE 203
- 9. CHROMIUM SUPPLEMENTATION IN HUMAN HEALTH, METABOLIC SYNDROME, AND DIABETES 231
- 10. MANGANESE: ITS ROLE IN DISEASE AND HEALTH 253
- 11. COBALT-SCHIFF BASE COMPLEXES: PRECLINICAL RESEARCH AND POTENTIAL THERAPEUTIC USES 267
- 12. COPPER DEPLETION AS A THERAPEUTIC STRATEGY IN CANCER 303
- 13. METAL COMPOUNDS IN THE DEVELOPMENT OF ANTIPARASITIC AGENTS: RATIONAL DESIGN FROM BASIC CHEMISTRY TO THE CLINIC 331
- 14. CHEMICAL AND CLINICAL ASPECTS OF METAL-CONTAINING ANTIDOTES FOR POISONING BY CYANIDE 359
- SUBJECT INDEX 393
Chapters in this book
- Frontmatter i
- About the Editors v
- Historical Development and Perspectives of the Series vii
- Preface to Volume 19 ix
- Contents xiii
- Contributors to Volume 19 xix
- Titles of Volumes 1–44 in the Metal Ions in Biological Systems Series xxiii
- Contents of Volumes in the Metal Ions in Life Sciences Series xxv
- 1. METALS IN MEDICINE: THE THERAPEUTIC USE OF METAL IONS IN THE CLINIC 1
- 2. SMALL MOLECULES: THE PAST OR THE FUTURE IN DRUG INNOVATION? 17
- 3. IRON CHELATION FOR IRON OVERLOAD IN THALASSEMIA 49
- 4. IRONING OUT THE BRAIN 87
- 5. INFECTIONS ASSOCIATED WITH IRON ADMINISTRATION 123
- 6. IRON OXIDE NANOPARTICLE FORMULATIONS FOR SUPPLEMENTATION 157
- 7. BUILDING A TROJAN HORSE: SIDEROPHORE-DRUG CONJUGATES FOR THE TREATMENT OF INFECTIOUS DISEASES 181
- 8. DEVELOPING VANADIUM AS AN ANTIDIABETIC OR ANTICANCER DRUG: A CLINICAL AND HISTORICAL PERSPECTIVE 203
- 9. CHROMIUM SUPPLEMENTATION IN HUMAN HEALTH, METABOLIC SYNDROME, AND DIABETES 231
- 10. MANGANESE: ITS ROLE IN DISEASE AND HEALTH 253
- 11. COBALT-SCHIFF BASE COMPLEXES: PRECLINICAL RESEARCH AND POTENTIAL THERAPEUTIC USES 267
- 12. COPPER DEPLETION AS A THERAPEUTIC STRATEGY IN CANCER 303
- 13. METAL COMPOUNDS IN THE DEVELOPMENT OF ANTIPARASITIC AGENTS: RATIONAL DESIGN FROM BASIC CHEMISTRY TO THE CLINIC 331
- 14. CHEMICAL AND CLINICAL ASPECTS OF METAL-CONTAINING ANTIDOTES FOR POISONING BY CYANIDE 359
- SUBJECT INDEX 393
