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16. COPPER COMPLEXES IN CANCER THERAPY

  • Delphine Denoyer , Sharnel A. S. Clatworthy und Michael A. Cater
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Metallo-Drugs: Development and Action of Anticancer Agents
Ein Kapitel aus dem Buch Metallo-Drugs: Development and Action of Anticancer Agents

Abstract

Copper homeostasis is tightly regulated in both prokaryotic and eukaryotic cells to ensure sufficient amounts for cuproprotein biosynthesis, while limiting oxidative stress production and toxicity. Over the last century, copper complexes have been developed as antimicrobials and for treating diseases involving copper dyshomeostasis (e.g., Wilson’s disease). There now exists a repertoire of copper complexes that can regulate bodily copper through a myriad of mechanisms. Furthermore, many copper complexes are now being appraised for a variety of therapeutic indications (e.g., Alzheimer’s disease and amyotrophic lateral sclerosis) that require a range of copper-related pharmacological affects. Cancer therapy is also drawing considerable attention since copper has been recognized as a limiting factor for multiple aspects of cancer progression including growth, angiogenesis, and metastasis. Consequently, ‘old copper complexes’ (e.g., tetrathiomolybdate and clioquinol) have been repurposed for cancer therapy and have demonstrated anticancer activity in vitro and in preclinical models. Likewise, new tailor-made copper complexes have been designed based on structural and biological features ideal for their anticancer activity. Human clinical trials continue to evaluate the therapeutic efficacy of copper complexes as anticancer agents and considerable progress has been made in understanding their pharmacological requirements. In this chapter, we present a historical perspective on the main copper complexes that are currently being repurposed for cancer therapy and detail several of the more recently developed compounds that have emerged as promising anticancer agents. We further provide an overview of the known mechanisms of action, including molecular targets and we discuss associated clinical trials.

Abstract

Copper homeostasis is tightly regulated in both prokaryotic and eukaryotic cells to ensure sufficient amounts for cuproprotein biosynthesis, while limiting oxidative stress production and toxicity. Over the last century, copper complexes have been developed as antimicrobials and for treating diseases involving copper dyshomeostasis (e.g., Wilson’s disease). There now exists a repertoire of copper complexes that can regulate bodily copper through a myriad of mechanisms. Furthermore, many copper complexes are now being appraised for a variety of therapeutic indications (e.g., Alzheimer’s disease and amyotrophic lateral sclerosis) that require a range of copper-related pharmacological affects. Cancer therapy is also drawing considerable attention since copper has been recognized as a limiting factor for multiple aspects of cancer progression including growth, angiogenesis, and metastasis. Consequently, ‘old copper complexes’ (e.g., tetrathiomolybdate and clioquinol) have been repurposed for cancer therapy and have demonstrated anticancer activity in vitro and in preclinical models. Likewise, new tailor-made copper complexes have been designed based on structural and biological features ideal for their anticancer activity. Human clinical trials continue to evaluate the therapeutic efficacy of copper complexes as anticancer agents and considerable progress has been made in understanding their pharmacological requirements. In this chapter, we present a historical perspective on the main copper complexes that are currently being repurposed for cancer therapy and detail several of the more recently developed compounds that have emerged as promising anticancer agents. We further provide an overview of the known mechanisms of action, including molecular targets and we discuss associated clinical trials.

Kapitel in diesem Buch

  1. Frontmatter i
  2. About the Editors v
  3. Historical Development and Perspectives of the Series vii
  4. Preface to Volume 18 ix
  5. Contents xiii
  6. Contributors to Volume 18 xix
  7. Titles of Volumes 1–44 in the Metal Ions in Biological Systems Series xxiii
  8. Contents of Volumes in the Metal Ions in Life Sciences Series xxv
  9. 1. CISPLATIN AND OXALIPLATIN: OUR CURRENT UNDERSTANDING OF THEIR ACTIONS 1
  10. 2. POLYNUCLEAR PLATINUM COMPLEXES. STRUCTURAL DIVERSITY AND DNA BINDING 43
  11. 3. PLATINUM(IV) PRODRUGS 69
  12. 4. METALLOGLYCOMICS 109
  13. 5. THE DECEPTIVELY SIMILAR RUTHENIUM(III) DRUG CANDIDATES KP1019 AND NAMI-A HAVE DIFFERENT ACTIONS. WHAT DID WE LEARN IN THE PAST 30 YEARS? 141
  14. 6. MULTINUCLEAR ORGANOMETALLIC RUTHENIUM-ARENE COMPLEXES FOR CANCER THERAPY 171
  15. 7. MEDICINAL CHEMISTRY OF GOLD ANTICANCER METALLODRUGS 199
  16. 8. COORDINATION COMPLEXES OF TITANIUM(IV) FOR ANTICANCER THERAPY 219
  17. 9. HEALTH BENEFITS OF VANADIUM AND ITS POTENTIAL AS AN ANTICANCER AGENT 251
  18. 10. GALLIUM COMPLEXES AS ANTICANCER DRUGS 281
  19. 11. NON-COVALENT METALLO-DRUGS: USING SHAPE TO TARGET DNA AND RNA JUNCTIONS AND OTHER NUCLEIC ACID STRUCTURES 303
  20. 12. NUCLEIC ACID QUADRUPLEXES AND METALLO-DRUGS 325
  21. 13. ANTITUMOR METALLODRUGS THAT TARGET PROTEINS 351
  22. 14. METALLOINTERCALATORS AND METALLOINSERTORS: STRUCTURAL REQUIREMENTS FOR DNA RECOGNITION AND ANTICANCER ACTIVITY 387
  23. 15. IRON AND ITS ROLE IN CANCER DEFENSE: A DOUBLE-EDGED SWORD 437
  24. 16. COPPER COMPLEXES IN CANCER THERAPY 469
  25. 17. TARGETING ZINC(II) SIGNALLING TO PREVENT CANCER 507
  26. SUBJECT INDEX 531
https://doi.org/10.1515/9783110470734-016

Kapitel in diesem Buch

  1. Frontmatter i
  2. About the Editors v
  3. Historical Development and Perspectives of the Series vii
  4. Preface to Volume 18 ix
  5. Contents xiii
  6. Contributors to Volume 18 xix
  7. Titles of Volumes 1–44 in the Metal Ions in Biological Systems Series xxiii
  8. Contents of Volumes in the Metal Ions in Life Sciences Series xxv
  9. 1. CISPLATIN AND OXALIPLATIN: OUR CURRENT UNDERSTANDING OF THEIR ACTIONS 1
  10. 2. POLYNUCLEAR PLATINUM COMPLEXES. STRUCTURAL DIVERSITY AND DNA BINDING 43
  11. 3. PLATINUM(IV) PRODRUGS 69
  12. 4. METALLOGLYCOMICS 109
  13. 5. THE DECEPTIVELY SIMILAR RUTHENIUM(III) DRUG CANDIDATES KP1019 AND NAMI-A HAVE DIFFERENT ACTIONS. WHAT DID WE LEARN IN THE PAST 30 YEARS? 141
  14. 6. MULTINUCLEAR ORGANOMETALLIC RUTHENIUM-ARENE COMPLEXES FOR CANCER THERAPY 171
  15. 7. MEDICINAL CHEMISTRY OF GOLD ANTICANCER METALLODRUGS 199
  16. 8. COORDINATION COMPLEXES OF TITANIUM(IV) FOR ANTICANCER THERAPY 219
  17. 9. HEALTH BENEFITS OF VANADIUM AND ITS POTENTIAL AS AN ANTICANCER AGENT 251
  18. 10. GALLIUM COMPLEXES AS ANTICANCER DRUGS 281
  19. 11. NON-COVALENT METALLO-DRUGS: USING SHAPE TO TARGET DNA AND RNA JUNCTIONS AND OTHER NUCLEIC ACID STRUCTURES 303
  20. 12. NUCLEIC ACID QUADRUPLEXES AND METALLO-DRUGS 325
  21. 13. ANTITUMOR METALLODRUGS THAT TARGET PROTEINS 351
  22. 14. METALLOINTERCALATORS AND METALLOINSERTORS: STRUCTURAL REQUIREMENTS FOR DNA RECOGNITION AND ANTICANCER ACTIVITY 387
  23. 15. IRON AND ITS ROLE IN CANCER DEFENSE: A DOUBLE-EDGED SWORD 437
  24. 16. COPPER COMPLEXES IN CANCER THERAPY 469
  25. 17. TARGETING ZINC(II) SIGNALLING TO PREVENT CANCER 507
  26. SUBJECT INDEX 531
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Heruntergeladen am 21.9.2025 von https://www.degruyterbrill.com/document/doi/10.1515/9783110470734-016/html
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