13. ANTITUMOR METALLODRUGS THAT TARGET PROTEINS
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Matthew P. Sullivan
Abstract
Anticancer platinum-based drugs are widely used in the treatment of a variety of tumorigenic diseases. They have been identified to target DNA and thereby induce apoptosis in cancer cells. Their reactivity to biomolecules other than DNA has often been associated with side effects that many cancer patients experience during chemotherapy. The development of metal compounds that target proteins rather than DNA has the potential to overcome or at least reduce the disadvantages of commonly used chemotherapeutics. Many exciting new metal complexes with novel modes of action have been reported and their anticancer activity was linked to selective protein interaction that may lead to improved accumulation in the tumor, higher selectivity and/or enhanced antiproliferative efficacy. The development of new lead structures requires bioanalytical methods to confirm the hypothesized modes of action or identify new, previously unexplored biological targets and pathways. We have selected original developments for review in this chapter and highlighted compounds on track toward clinical application.
Abstract
Anticancer platinum-based drugs are widely used in the treatment of a variety of tumorigenic diseases. They have been identified to target DNA and thereby induce apoptosis in cancer cells. Their reactivity to biomolecules other than DNA has often been associated with side effects that many cancer patients experience during chemotherapy. The development of metal compounds that target proteins rather than DNA has the potential to overcome or at least reduce the disadvantages of commonly used chemotherapeutics. Many exciting new metal complexes with novel modes of action have been reported and their anticancer activity was linked to selective protein interaction that may lead to improved accumulation in the tumor, higher selectivity and/or enhanced antiproliferative efficacy. The development of new lead structures requires bioanalytical methods to confirm the hypothesized modes of action or identify new, previously unexplored biological targets and pathways. We have selected original developments for review in this chapter and highlighted compounds on track toward clinical application.
Kapitel in diesem Buch
- Frontmatter i
- About the Editors v
- Historical Development and Perspectives of the Series vii
- Preface to Volume 18 ix
- Contents xiii
- Contributors to Volume 18 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. CISPLATIN AND OXALIPLATIN: OUR CURRENT UNDERSTANDING OF THEIR ACTIONS 1
- 2. POLYNUCLEAR PLATINUM COMPLEXES. STRUCTURAL DIVERSITY AND DNA BINDING 43
- 3. PLATINUM(IV) PRODRUGS 69
- 4. METALLOGLYCOMICS 109
- 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
- 6. MULTINUCLEAR ORGANOMETALLIC RUTHENIUM-ARENE COMPLEXES FOR CANCER THERAPY 171
- 7. MEDICINAL CHEMISTRY OF GOLD ANTICANCER METALLODRUGS 199
- 8. COORDINATION COMPLEXES OF TITANIUM(IV) FOR ANTICANCER THERAPY 219
- 9. HEALTH BENEFITS OF VANADIUM AND ITS POTENTIAL AS AN ANTICANCER AGENT 251
- 10. GALLIUM COMPLEXES AS ANTICANCER DRUGS 281
- 11. NON-COVALENT METALLO-DRUGS: USING SHAPE TO TARGET DNA AND RNA JUNCTIONS AND OTHER NUCLEIC ACID STRUCTURES 303
- 12. NUCLEIC ACID QUADRUPLEXES AND METALLO-DRUGS 325
- 13. ANTITUMOR METALLODRUGS THAT TARGET PROTEINS 351
- 14. METALLOINTERCALATORS AND METALLOINSERTORS: STRUCTURAL REQUIREMENTS FOR DNA RECOGNITION AND ANTICANCER ACTIVITY 387
- 15. IRON AND ITS ROLE IN CANCER DEFENSE: A DOUBLE-EDGED SWORD 437
- 16. COPPER COMPLEXES IN CANCER THERAPY 469
- 17. TARGETING ZINC(II) SIGNALLING TO PREVENT CANCER 507
- SUBJECT INDEX 531
Kapitel in diesem Buch
- Frontmatter i
- About the Editors v
- Historical Development and Perspectives of the Series vii
- Preface to Volume 18 ix
- Contents xiii
- Contributors to Volume 18 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. CISPLATIN AND OXALIPLATIN: OUR CURRENT UNDERSTANDING OF THEIR ACTIONS 1
- 2. POLYNUCLEAR PLATINUM COMPLEXES. STRUCTURAL DIVERSITY AND DNA BINDING 43
- 3. PLATINUM(IV) PRODRUGS 69
- 4. METALLOGLYCOMICS 109
- 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
- 6. MULTINUCLEAR ORGANOMETALLIC RUTHENIUM-ARENE COMPLEXES FOR CANCER THERAPY 171
- 7. MEDICINAL CHEMISTRY OF GOLD ANTICANCER METALLODRUGS 199
- 8. COORDINATION COMPLEXES OF TITANIUM(IV) FOR ANTICANCER THERAPY 219
- 9. HEALTH BENEFITS OF VANADIUM AND ITS POTENTIAL AS AN ANTICANCER AGENT 251
- 10. GALLIUM COMPLEXES AS ANTICANCER DRUGS 281
- 11. NON-COVALENT METALLO-DRUGS: USING SHAPE TO TARGET DNA AND RNA JUNCTIONS AND OTHER NUCLEIC ACID STRUCTURES 303
- 12. NUCLEIC ACID QUADRUPLEXES AND METALLO-DRUGS 325
- 13. ANTITUMOR METALLODRUGS THAT TARGET PROTEINS 351
- 14. METALLOINTERCALATORS AND METALLOINSERTORS: STRUCTURAL REQUIREMENTS FOR DNA RECOGNITION AND ANTICANCER ACTIVITY 387
- 15. IRON AND ITS ROLE IN CANCER DEFENSE: A DOUBLE-EDGED SWORD 437
- 16. COPPER COMPLEXES IN CANCER THERAPY 469
- 17. TARGETING ZINC(II) SIGNALLING TO PREVENT CANCER 507
- SUBJECT INDEX 531
