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This book presents an overview of cancer and the genesis, and development of different treatment strategies and modalities against cancer. The emergence of gold and its complexes as promising anticancer chemotherapeutic agents have the potential to substitute or replace the platinum based chemotherapeutic agents. Gold complexes have demonstrated considerable anti-proliferative properties, chiefly attributed to their anti-mitochondrial effects, they make gold complexes excellent candidates as anti-cancer agents compared to their platinum-based counterparts. This book provides a critical review of recent advances made in the development of gold complexes as anti-cancer agents. In this context, it examines a number of different ligand architectures, provides comprehensive information on gold complexes’ mechanism of action and toxicity issues and, in closing, outlines future research directions.
Book Synopsis Gold and its Complexes in Anticancer Chemotherapy by : Mohmmad Younus Wani
Download or read book Gold and its Complexes in Anticancer Chemotherapy written by Mohmmad Younus Wani and published by Springer Nature. This book was released on 2021-02-11 with total page 173 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book presents an overview of cancer and the genesis, and development of different treatment strategies and modalities against cancer. The emergence of gold and its complexes as promising anticancer chemotherapeutic agents have the potential to substitute or replace the platinum based chemotherapeutic agents. Gold complexes have demonstrated considerable anti-proliferative properties, chiefly attributed to their anti-mitochondrial effects, they make gold complexes excellent candidates as anti-cancer agents compared to their platinum-based counterparts. This book provides a critical review of recent advances made in the development of gold complexes as anti-cancer agents. In this context, it examines a number of different ligand architectures, provides comprehensive information on gold complexes’ mechanism of action and toxicity issues and, in closing, outlines future research directions.
This book is organized into 12 important chapters that focus on the progress made by metal-based drugs as anticancer, antibacterial, antiviral, anti-inflammatory, and anti-neurodegenerative agents, as well as highlights the application areas of newly discovered metallodrugs. It can prove beneficial for researchers, investigators and scientists whose work involves inorganic and coordination chemistry, medical science, pharmacy, biotechnology and biomedical engineering.
Book Synopsis Advances in Metallodrugs by : Shahid Ul-Islam
Download or read book Advances in Metallodrugs written by Shahid Ul-Islam and published by John Wiley & Sons. This book was released on 2020-07-08 with total page 432 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is organized into 12 important chapters that focus on the progress made by metal-based drugs as anticancer, antibacterial, antiviral, anti-inflammatory, and anti-neurodegenerative agents, as well as highlights the application areas of newly discovered metallodrugs. It can prove beneficial for researchers, investigators and scientists whose work involves inorganic and coordination chemistry, medical science, pharmacy, biotechnology and biomedical engineering.
Volume 18, entitled Metallo-Drugs: Development and Action of Anticancer Agents of the series Metal Ions in Life Sciences centers on biological, medicinal inorganic chemistry. The serendipitous discovery of the antitumor activity of cis-diamminodichloroplatinum(II) (cisplatin) by Barnett Rosenberg in the 1960s is a landmark in metallodrug-based chemotherapy. The success of cisplatin in the clinic, followed by oxaliplatin and carboplatin, along with their drawbacks relating mainly to resistance development and severe toxicity, initiated research on polynuclear platinum complexes and on Pt(IV) complexes as prodrugs. Furthermore, the indicated shortcomings led to the exploration of other transition and main group metal ions, among them Ru(II/III), Au(I/III), Ti(IV), V(IV/V), and Ga(III) including also the essential metal ions Fe(II/III), Cu(I/II), and Zn(II). Ionic as well as covalent and non-covalent interactions between structurally very different complexes and biomolecules like nucleic acids, proteins, and carbohydrates are studied and discussed with regard to their possible anticancer actions. Hence, MILS-18 summarizes the research at the forefront of medicinal inorganic chemistry, including studies on the next-generation, tailor-made anticancer drugs. All this and more is treated in an authoritative and timely manner in the 17 stimulating chapters of this book, written by 39 internationally recognized experts from 10 nations (from the US via Europe to China and Australia). The impact of this vibrant research area is manifested by more than 2700 references, nearly 150 illustrations (more than half in color) and several comprehensive tables. Metallo-Drugs: Development and Action of Anticancer Agents is an essential resource for scientists working in the wide range from enzymology, material sciences, analytical, organic, and inorganic biochemistry all the way through to medicine including the clinic ... not forgetting that it also provides excellent information for teaching.
Book Synopsis Metallo-Drugs: Development and Action of Anticancer Agents by : Astrid Sigel
Download or read book Metallo-Drugs: Development and Action of Anticancer Agents written by Astrid Sigel and published by Walter de Gruyter GmbH & Co KG. This book was released on 2018-02-05 with total page 588 pages. Available in PDF, EPUB and Kindle. Book excerpt: Volume 18, entitled Metallo-Drugs: Development and Action of Anticancer Agents of the series Metal Ions in Life Sciences centers on biological, medicinal inorganic chemistry. The serendipitous discovery of the antitumor activity of cis-diamminodichloroplatinum(II) (cisplatin) by Barnett Rosenberg in the 1960s is a landmark in metallodrug-based chemotherapy. The success of cisplatin in the clinic, followed by oxaliplatin and carboplatin, along with their drawbacks relating mainly to resistance development and severe toxicity, initiated research on polynuclear platinum complexes and on Pt(IV) complexes as prodrugs. Furthermore, the indicated shortcomings led to the exploration of other transition and main group metal ions, among them Ru(II/III), Au(I/III), Ti(IV), V(IV/V), and Ga(III) including also the essential metal ions Fe(II/III), Cu(I/II), and Zn(II). Ionic as well as covalent and non-covalent interactions between structurally very different complexes and biomolecules like nucleic acids, proteins, and carbohydrates are studied and discussed with regard to their possible anticancer actions. Hence, MILS-18 summarizes the research at the forefront of medicinal inorganic chemistry, including studies on the next-generation, tailor-made anticancer drugs. All this and more is treated in an authoritative and timely manner in the 17 stimulating chapters of this book, written by 39 internationally recognized experts from 10 nations (from the US via Europe to China and Australia). The impact of this vibrant research area is manifested by more than 2700 references, nearly 150 illustrations (more than half in color) and several comprehensive tables. Metallo-Drugs: Development and Action of Anticancer Agents is an essential resource for scientists working in the wide range from enzymology, material sciences, analytical, organic, and inorganic biochemistry all the way through to medicine including the clinic ... not forgetting that it also provides excellent information for teaching.
This thesis focuses on the development of gold- and non-classical platinum-based anti-cancer agents that display distinctively different anti-cancer mechanisms compared to the commonly used cisplatin. These metal complexes contain N-heterocyclic carbene (NHC) ligands which are able to form strong M-C(NHC) bonds, conferring high stability and favorable lipophilicity, reactivity and binding specificity of metal complexes on biomolecules. The author demonstrates significant advances made in anti-cancer gold(III), gold(I) and platinum(II) complexes. Detailed chemical synthesis, in vitro and/or in vivo anti-cancer activities are clearly presented including: (i) a class of Au(III) complexes containing a highly fluorescent N^N^N ligand and NHC ligand that simultaneously act as fluorescent thiol “switch-on” probes and anti-cancer agents; (ii) a dinuclear gold(I) complex with a mixed diphosphine and bis(NHC) ligand displaying favorable stability and showing significant inhibition of tumor growth in two independent mice models with no observable side effects; and (iii) a panel of stable luminescent cyclometalated platinum(II) complexes exhibiting high specificity to localize to the endoplasmic reticulum (ER) domain, inducing ER stress and cell apoptosis. These works highlight the clinical potential that gold and platinum complexes offer for cancer treatment.
Book Synopsis Anti-Cancer N-Heterocyclic Carbene Complexes of Gold(III), Gold(I) and Platinum(II) by : Taotao Zou
Download or read book Anti-Cancer N-Heterocyclic Carbene Complexes of Gold(III), Gold(I) and Platinum(II) written by Taotao Zou and published by Springer. This book was released on 2016-02-19 with total page 175 pages. Available in PDF, EPUB and Kindle. Book excerpt: This thesis focuses on the development of gold- and non-classical platinum-based anti-cancer agents that display distinctively different anti-cancer mechanisms compared to the commonly used cisplatin. These metal complexes contain N-heterocyclic carbene (NHC) ligands which are able to form strong M-C(NHC) bonds, conferring high stability and favorable lipophilicity, reactivity and binding specificity of metal complexes on biomolecules. The author demonstrates significant advances made in anti-cancer gold(III), gold(I) and platinum(II) complexes. Detailed chemical synthesis, in vitro and/or in vivo anti-cancer activities are clearly presented including: (i) a class of Au(III) complexes containing a highly fluorescent N^N^N ligand and NHC ligand that simultaneously act as fluorescent thiol “switch-on” probes and anti-cancer agents; (ii) a dinuclear gold(I) complex with a mixed diphosphine and bis(NHC) ligand displaying favorable stability and showing significant inhibition of tumor growth in two independent mice models with no observable side effects; and (iii) a panel of stable luminescent cyclometalated platinum(II) complexes exhibiting high specificity to localize to the endoplasmic reticulum (ER) domain, inducing ER stress and cell apoptosis. These works highlight the clinical potential that gold and platinum complexes offer for cancer treatment.
This dissertation, "Anti-cancer N-heterocyclic Carbene Complexes of Gold(III), Gold(I) and Platinum(II): Thiol "switch-on" Fluorescent Probes, Thioredoxin Reductase Inhibitors and Endoplasmic Reticulum Targeting Agents" by Taotao, Zou, 邹滔滔, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled "Anti-Cancer N-Heterocyclic Carbene Complexes of Gold(III), Gold(I) and Platinum(II): Thiol "Switch-on" Fluorescent Probes, Thioredoxin Reductase Inhibitors and Endoplasmic Reticulum Targeting Agents" Submitted by ZOU TAOTAO for the degree of Doctor of Philosophy at The University of Hong Kong in Feb 2015 Despite the success of cisplatin in combating various cancers, the problems of resistance and side effects have limited its wide application in cancer treatment. Gold complexes have recently emerged as promising candidates for cancer treatment. Unlike cisplatin, gold complexes do not favor DNA binding, but instead preferentially bind SH/SeH-containing proteins/enzymes in cancer cells, giving hope that these compounds may overcome cisplatin's resistance problems. Since the side effects of cisplatin are, at least partially, caused by instability-associated, off-target binding interactions, the incorporation of N-heterocyclic carbene (NHC) ligands may be a useful strategy to improve the stability of metal-based chemotherapeutics due to the strong donating ability of NHC to form strong M-C(NHC) bonds. Meanwhile, the ease of modification and steric effects of NHC ligands provide favorable lipophilicity, reactivity and binding specificity of metal complexes. Indeed, some Pt(II)-NHC complexes have been reported to specifically target proteins/organelles rather than DNA. 3+ + The reduction of 4-coordinated Au to 2-coordinated Au by thiols has been 3+ demonstrated. Meanwhile, owing to the low energy d 2 2 orbital of Au, most gold(III) x -y complexes are non-emissive in solutions. In Chapter 3, by taking advantage of these unique properties, the synthesis of a class of non-emissive Au(III) complexes containing highly fluorescent N DEGREESN DEGREESN ligands and NHC ligands is described. In these compounds, the NHC ligand prevented further reduction of Au(III) to Au(0) and increased the III + solubility of the Au(III) complexes. The [Au (N DEGREESN DEGREESN)(NHC)] complex was readily reduced by GSH to form [Au (NHC)(GS)], accompanied by the release of the fluorescent H N DEGREESN DEGREESN ligand, therefore acting as a fluorescent "switch-on" probe for thiols. In addition, the anti-cancer activity of Au(I) is owed to its ability to inhibit thiol-enzymes; thus, the Au(III) complexes could also serve as precursors/prodrugs, activated by metal reduction, to deliver anti-cancer active Au(I) species. The major problem of most Au(I) anti-cancer agents is the lack of in vivo anti-tumor activity due to their high thiol-reactivity which leads to many off-target binding interactions with blood thiols. In Chapter 4, the synthesis of a dinuclear gold(I) complex bearing a mixed diphosphine and bis(NHC) ligand is described. This dinuclear Au(I) complex displayed a favorable stability that conveys potent thioredoxin reductase inhibition without being attacked by blood thiols. This complex significantly inhibited tumor growth in two independent mouse models with no observable side effects. The dinuclear Au(I) complex also exhibited anti-angiogenesis activity in a tumor model and inhibited sphere formation of cancer stem cells in vitro. In toxicology studies, neither systemic anaphylaxis in guinea pigs nor localized irritation in rabbits was observed
Book Synopsis Anti-Cancer N-Heterocyclic Carbene Complexes of Gold(iii), Gold(i) and Platinum(ii) by : Taotao Zou
Download or read book Anti-Cancer N-Heterocyclic Carbene Complexes of Gold(iii), Gold(i) and Platinum(ii) written by Taotao Zou and published by Open Dissertation Press. This book was released on 2017-01-27 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: This dissertation, "Anti-cancer N-heterocyclic Carbene Complexes of Gold(III), Gold(I) and Platinum(II): Thiol "switch-on" Fluorescent Probes, Thioredoxin Reductase Inhibitors and Endoplasmic Reticulum Targeting Agents" by Taotao, Zou, 邹滔滔, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled "Anti-Cancer N-Heterocyclic Carbene Complexes of Gold(III), Gold(I) and Platinum(II): Thiol "Switch-on" Fluorescent Probes, Thioredoxin Reductase Inhibitors and Endoplasmic Reticulum Targeting Agents" Submitted by ZOU TAOTAO for the degree of Doctor of Philosophy at The University of Hong Kong in Feb 2015 Despite the success of cisplatin in combating various cancers, the problems of resistance and side effects have limited its wide application in cancer treatment. Gold complexes have recently emerged as promising candidates for cancer treatment. Unlike cisplatin, gold complexes do not favor DNA binding, but instead preferentially bind SH/SeH-containing proteins/enzymes in cancer cells, giving hope that these compounds may overcome cisplatin's resistance problems. Since the side effects of cisplatin are, at least partially, caused by instability-associated, off-target binding interactions, the incorporation of N-heterocyclic carbene (NHC) ligands may be a useful strategy to improve the stability of metal-based chemotherapeutics due to the strong donating ability of NHC to form strong M-C(NHC) bonds. Meanwhile, the ease of modification and steric effects of NHC ligands provide favorable lipophilicity, reactivity and binding specificity of metal complexes. Indeed, some Pt(II)-NHC complexes have been reported to specifically target proteins/organelles rather than DNA. 3+ + The reduction of 4-coordinated Au to 2-coordinated Au by thiols has been 3+ demonstrated. Meanwhile, owing to the low energy d 2 2 orbital of Au, most gold(III) x -y complexes are non-emissive in solutions. In Chapter 3, by taking advantage of these unique properties, the synthesis of a class of non-emissive Au(III) complexes containing highly fluorescent N DEGREESN DEGREESN ligands and NHC ligands is described. In these compounds, the NHC ligand prevented further reduction of Au(III) to Au(0) and increased the III + solubility of the Au(III) complexes. The [Au (N DEGREESN DEGREESN)(NHC)] complex was readily reduced by GSH to form [Au (NHC)(GS)], accompanied by the release of the fluorescent H N DEGREESN DEGREESN ligand, therefore acting as a fluorescent "switch-on" probe for thiols. In addition, the anti-cancer activity of Au(I) is owed to its ability to inhibit thiol-enzymes; thus, the Au(III) complexes could also serve as precursors/prodrugs, activated by metal reduction, to deliver anti-cancer active Au(I) species. The major problem of most Au(I) anti-cancer agents is the lack of in vivo anti-tumor activity due to their high thiol-reactivity which leads to many off-target binding interactions with blood thiols. In Chapter 4, the synthesis of a dinuclear gold(I) complex bearing a mixed diphosphine and bis(NHC) ligand is described. This dinuclear Au(I) complex displayed a favorable stability that conveys potent thioredoxin reductase inhibition without being attacked by blood thiols. This complex significantly inhibited tumor growth in two independent mouse models with no observable side effects. The dinuclear Au(I) complex also exhibited anti-angiogenesis activity in a tumor model and inhibited sphere formation of cancer stem cells in vitro. In toxicology studies, neither systemic anaphylaxis in guinea pigs nor localized irritation in rabbits was observed
Metal-based anticancer drugs are among the most successful therapeutic agents, as evidenced by the frequent prescription of selected platinum and arsenic compounds to patients. Metal-based Anticancer Agents covers the interdisciplinary world of inorganic drug discovery and development by introducing the most prominent compound classes based on different transition metals, discussing emerging concepts and enabling methods, as well as presenting key pre-clinical and clinical aspects. Recent progress on the unique features of next-generation targeted metal-based anticancer agents, including supramolecular coordination complexes used for both therapy and drug delivery, promise a bright future beyond the benefits of pure cytotoxic activity. With contributions from global leaders in the field, this book will serve as a useful reference to established researchers as well as a practical guide to those new to metallodrugs, and postgraduate students of medicinal chemistry and metallobiology.
Book Synopsis Metal-based Anticancer Agents by : Angela Casini
Download or read book Metal-based Anticancer Agents written by Angela Casini and published by Royal Society of Chemistry. This book was released on 2019-04-23 with total page 370 pages. Available in PDF, EPUB and Kindle. Book excerpt: Metal-based anticancer drugs are among the most successful therapeutic agents, as evidenced by the frequent prescription of selected platinum and arsenic compounds to patients. Metal-based Anticancer Agents covers the interdisciplinary world of inorganic drug discovery and development by introducing the most prominent compound classes based on different transition metals, discussing emerging concepts and enabling methods, as well as presenting key pre-clinical and clinical aspects. Recent progress on the unique features of next-generation targeted metal-based anticancer agents, including supramolecular coordination complexes used for both therapy and drug delivery, promise a bright future beyond the benefits of pure cytotoxic activity. With contributions from global leaders in the field, this book will serve as a useful reference to established researchers as well as a practical guide to those new to metallodrugs, and postgraduate students of medicinal chemistry and metallobiology.
This dissertation, "The Anti-cancer Properties of Cyclometalated Gold(III) Complexes and Organogold(III) Supramolecular Polymers" by Jingjing, Zhang, 张晶晶, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Prompted by the successful clinical application of cisplatin in cancer therapy, worldwide efforts have been devoted to develop new metal-based drugs for anticancer treatment. Gold(III) complexes at first received attention as anti-cancer drug candidates because of their square-planar geometry which resembles that of platinum(II) complexes. Subsequent studies revealed that various gold(III) complexes displayed promising anti-cancer activities with different biological mechanisms. Although some achievements have been obtained in the development of anti-cancer gold(III) complexes, challenges including the improvement of bioavailability, stability and selectivity, elucidation of the action mechanisms, and the development of novel delivery approaches of gold(III) complexes to reduce systematic toxicity, remain to be exploited. A panel of anti-cancer complexes [AuIII(R-C DEGREESN)(L)]n+ (wherein HC DEGREESN is 2-phenylpyridine, L is biguanide or biuret) have been identified and described in Chapter 3. Biguanide or biuret have been employed to improve the solubility of the complexes in aqueous solutions. Meanwhile, the lipophilicity could readily be adjusted by varying the R group to obtain a balance between lipophilicity and aqueous solubility. Among the synthesized complexes, the cationic complexes, [AuIII(butyl-C DEGREESN)biguanide]Cl (3.1) and [AuIII(C DEGREESN)biguanide]Cl (3.2) are soluble in aqueous solutions with solubility over 5 mg/mL. Besides, introduction of butyl groups to 3.1 and [AuIII(butyl-C DEGREESN)biuret] (3.3) resulted in higher cellular uptake of gold, which might enhance their cytotoxic activities (IC50 values: 1.5-17 μM) compared with 3.2 and [AuIII(C DEGREESN)biuret] (3.4) (IC50 values: 9.4-47.3 μM). Moreover, 3.1 was also found to induce cell cycle arrest in S-phase and endoplasmic reticulum (ER) damage in human cervical epithelial carcinoma (HeLa) cells, and display significant anti-angiogenic activity at its sub-cytotoxic concentrations. In Chapter 4, a series of gold(III) complexes with dithiocarbamate and 2-phenylpyridine ligands to target deubiquitinases (DUBs), have been designed. These complexes achieved significant inhibition on purified DUBs. Notably, [AuIII(2-(4-nbutylphenyl) pyridyl)(diethyldithiocarbamate)]PF6 (4.1) inhibited both the purified (IC50 values: 46-223 nM) and cell-based DUBs activities with high efficiency. Its interaction with DUB UCHL1 and peptides which are present in several types of DUBs and contain active cysteine residue were confirmed by mass spectrometric analysis. All complexes displayed significant cytotoxicities, and those containing diethyldithiocarbamate ligand displayed specific cytotoxicity on breast cancer cells. Accumulation of a tumor suppressor p53, cell-cycle arrest, and apoptotic cell death were induced in breast cancer cells by 4.1. Besides, 4.1 also showed anti-angiogenic effects. These biological activities might be related with DUBs inhibition. In Chapter 5, a cytotoxic complex [AuIII(C DEGREESN DEGREESC)(4-dpt)](CF3SO3) (5.1, HC DEGREESN DEGREESCH = 2,6-diphenylpyridine; 4-dpt = 2,4-diamino-6-(4-pyridyl)-1,3,5-triazine) has been designed to self-assemble into supramolecular polymers (5.1-SP) in acetonitrile. In physiologically relevant solutions, 5.1-SP displayed a sustained-release property of the anti-angiogenic ligand 4-dpt, and in the presence of glutathione (GSH), [AuIII(C DEGREESN D
Book Synopsis The Anti-Cancer Properties of Cyclometalated Gold(iii) Complexes and Organogold(iii) Supramolecular Polymers by : Jingjing Zhang
Download or read book The Anti-Cancer Properties of Cyclometalated Gold(iii) Complexes and Organogold(iii) Supramolecular Polymers written by Jingjing Zhang and published by Open Dissertation Press. This book was released on 2017-01-27 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: This dissertation, "The Anti-cancer Properties of Cyclometalated Gold(III) Complexes and Organogold(III) Supramolecular Polymers" by Jingjing, Zhang, 张晶晶, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Prompted by the successful clinical application of cisplatin in cancer therapy, worldwide efforts have been devoted to develop new metal-based drugs for anticancer treatment. Gold(III) complexes at first received attention as anti-cancer drug candidates because of their square-planar geometry which resembles that of platinum(II) complexes. Subsequent studies revealed that various gold(III) complexes displayed promising anti-cancer activities with different biological mechanisms. Although some achievements have been obtained in the development of anti-cancer gold(III) complexes, challenges including the improvement of bioavailability, stability and selectivity, elucidation of the action mechanisms, and the development of novel delivery approaches of gold(III) complexes to reduce systematic toxicity, remain to be exploited. A panel of anti-cancer complexes [AuIII(R-C DEGREESN)(L)]n+ (wherein HC DEGREESN is 2-phenylpyridine, L is biguanide or biuret) have been identified and described in Chapter 3. Biguanide or biuret have been employed to improve the solubility of the complexes in aqueous solutions. Meanwhile, the lipophilicity could readily be adjusted by varying the R group to obtain a balance between lipophilicity and aqueous solubility. Among the synthesized complexes, the cationic complexes, [AuIII(butyl-C DEGREESN)biguanide]Cl (3.1) and [AuIII(C DEGREESN)biguanide]Cl (3.2) are soluble in aqueous solutions with solubility over 5 mg/mL. Besides, introduction of butyl groups to 3.1 and [AuIII(butyl-C DEGREESN)biuret] (3.3) resulted in higher cellular uptake of gold, which might enhance their cytotoxic activities (IC50 values: 1.5-17 μM) compared with 3.2 and [AuIII(C DEGREESN)biuret] (3.4) (IC50 values: 9.4-47.3 μM). Moreover, 3.1 was also found to induce cell cycle arrest in S-phase and endoplasmic reticulum (ER) damage in human cervical epithelial carcinoma (HeLa) cells, and display significant anti-angiogenic activity at its sub-cytotoxic concentrations. In Chapter 4, a series of gold(III) complexes with dithiocarbamate and 2-phenylpyridine ligands to target deubiquitinases (DUBs), have been designed. These complexes achieved significant inhibition on purified DUBs. Notably, [AuIII(2-(4-nbutylphenyl) pyridyl)(diethyldithiocarbamate)]PF6 (4.1) inhibited both the purified (IC50 values: 46-223 nM) and cell-based DUBs activities with high efficiency. Its interaction with DUB UCHL1 and peptides which are present in several types of DUBs and contain active cysteine residue were confirmed by mass spectrometric analysis. All complexes displayed significant cytotoxicities, and those containing diethyldithiocarbamate ligand displayed specific cytotoxicity on breast cancer cells. Accumulation of a tumor suppressor p53, cell-cycle arrest, and apoptotic cell death were induced in breast cancer cells by 4.1. Besides, 4.1 also showed anti-angiogenic effects. These biological activities might be related with DUBs inhibition. In Chapter 5, a cytotoxic complex [AuIII(C DEGREESN DEGREESC)(4-dpt)](CF3SO3) (5.1, HC DEGREESN DEGREESCH = 2,6-diphenylpyridine; 4-dpt = 2,4-diamino-6-(4-pyridyl)-1,3,5-triazine) has been designed to self-assemble into supramolecular polymers (5.1-SP) in acetonitrile. In physiologically relevant solutions, 5.1-SP displayed a sustained-release property of the anti-angiogenic ligand 4-dpt, and in the presence of glutathione (GSH), [AuIII(C DEGREESN D
The discovery of the antitumour activity of cisplatin in 1965 and its subsequent introduction into clinical trials in 1971 was the catalyst for a major international research effort investigating the potential of metal compounds in cancer therapy. Cisplatin now occupies an important place in the armamentarium of the oncologist due to its effectiveness in the treatment of testicular cancer. A second generation analogue, carbo platin, offers reduced toxicity together with therapeutic activity, which gives it a place in the front-line therapy of genitourinary cancers. These and other successes have encouraged the search for novel metal-based drugs for cancer therapy. Research has shown that metal compounds have potential for activity not only as cytotoxic antitumour agents, but also in areas such as adjuvant therapy, diagnosis and immunotherapy. The aim of this book is to review and describe the major achievements and developments arising from this international research effort. The contributing authors come from labora tories throughout Europe and America and represent the many disci plines characteristic of this research, such as clinical research, pharmacology, tumour biology and inorganic medicinal chemistry.
Book Synopsis Metal Compounds in Cancer Therapy by : S.P. Fricker
Download or read book Metal Compounds in Cancer Therapy written by S.P. Fricker and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 269 pages. Available in PDF, EPUB and Kindle. Book excerpt: The discovery of the antitumour activity of cisplatin in 1965 and its subsequent introduction into clinical trials in 1971 was the catalyst for a major international research effort investigating the potential of metal compounds in cancer therapy. Cisplatin now occupies an important place in the armamentarium of the oncologist due to its effectiveness in the treatment of testicular cancer. A second generation analogue, carbo platin, offers reduced toxicity together with therapeutic activity, which gives it a place in the front-line therapy of genitourinary cancers. These and other successes have encouraged the search for novel metal-based drugs for cancer therapy. Research has shown that metal compounds have potential for activity not only as cytotoxic antitumour agents, but also in areas such as adjuvant therapy, diagnosis and immunotherapy. The aim of this book is to review and describe the major achievements and developments arising from this international research effort. The contributing authors come from labora tories throughout Europe and America and represent the many disci plines characteristic of this research, such as clinical research, pharmacology, tumour biology and inorganic medicinal chemistry.
30 years after its discovery as an antitumor agent, cisplatin represents today one of the most successful drugs in chemotherapy. This book is intended to reminisce this event, to take inventory, and to point out new lines of development in this field. Divided in 6 sections and 22 chapters, the book provides an up-to-date account on topics such as - the chemistry and biochemistry of cisplatin, - the clinical status of Pt anticancer drugs, - the impact of cisplatin on inorganic and coordination chemistry, - new developments in drug design, testing and delivery. It also includes a chapter describing the historical development of the discovery of cisplatin. The ultimate question - How does cisplatin kill a cell? - is yet to be answered, but there are now new links suggesting how Pt binding to DNA may trigger a cascade of cellular reactions that eventually result in apoptosis. p53 and a series of damage recognition proteins of the HMG-domain family appear to be involved. The book addresses the problem of mutagenicity of Pt drugs and raises the question of the possible relevance of the minor DNA adducts, e.g. of interstrand cross-links, and the possible use of trans-(NH3)2Pt(II)-modified oligonucleotides in antisense and antigene strategies. Our present understanding of reactions of cisplatin with DNA is based upon numerous model studies (from isolated model nucleobases to short DNA fragments) and application of a large body of spectroscopic and other physico-chemical techniques. Thanks to these efforts there is presently no other metal ion whose reactions with nucleic acids are better understood than Pt. In a series of chapters, basic studies on the interactions of Pt electrophiles with nucleobases, oligonucleotides, DNA, amino acids, peptides and proteins are reported, which use, among others, sophisticated NMR techniques or X-ray crystallography, to get remarkable understanding of details on such reactions. Reactivity of cisplatin, once bound to DNA and formerly believed to be inert enough to stay, is an emerging phenomenon. It has (not yet) widely been studied but is potentially extremely important. Medicinal bioinorganic chemistry - the role of metal compounds in medicine - has received an enormous boost from cisplatin, and so has bioinorganic chemistry as a whole. There is hardly a better example than cisplatin to demonstrate what bioinorganic chemistry is all about: The marriage between classic inorganic (coordination) chemistry and the other life sciences - medicine, pharmacy, biology, biochemistry. Cisplatin has left its mark also on areas that are generally considered largely inorganic. The subject of mixed-valance Pt compounds is an example: From the sleeping beauty it made its way to the headlines of scientific journals, thanks to a class of novel Pt antitumor agents, the so-called "platinum pyrimidine blues". In the aftermath diplatinum (III) compounds were recognized and studies in large numbers, and now an organometalic chemistry of these diplatinum (III) species is beginning to emerge. The final section of the book is concerned with new developments such as novel di- and trinuclear Pt(II) drugs with DNA binding properties different from those of cisplatin, with orally active Pt(IV) drugs which are presently in clinical studies, and with attempts to modify combinatorial chemistry in such a way that it may become applicable to fast screening of Pt antitumor drugs. The potential of including computational methods in solving questions of Pt-DNA interactions is critically dealt with in the concluding chapter.
Book Synopsis Cisplatin by : Bernhard Lippert
Download or read book Cisplatin written by Bernhard Lippert and published by John Wiley & Sons. This book was released on 1999 with total page 628 pages. Available in PDF, EPUB and Kindle. Book excerpt: 30 years after its discovery as an antitumor agent, cisplatin represents today one of the most successful drugs in chemotherapy. This book is intended to reminisce this event, to take inventory, and to point out new lines of development in this field. Divided in 6 sections and 22 chapters, the book provides an up-to-date account on topics such as - the chemistry and biochemistry of cisplatin, - the clinical status of Pt anticancer drugs, - the impact of cisplatin on inorganic and coordination chemistry, - new developments in drug design, testing and delivery. It also includes a chapter describing the historical development of the discovery of cisplatin. The ultimate question - How does cisplatin kill a cell? - is yet to be answered, but there are now new links suggesting how Pt binding to DNA may trigger a cascade of cellular reactions that eventually result in apoptosis. p53 and a series of damage recognition proteins of the HMG-domain family appear to be involved. The book addresses the problem of mutagenicity of Pt drugs and raises the question of the possible relevance of the minor DNA adducts, e.g. of interstrand cross-links, and the possible use of trans-(NH3)2Pt(II)-modified oligonucleotides in antisense and antigene strategies. Our present understanding of reactions of cisplatin with DNA is based upon numerous model studies (from isolated model nucleobases to short DNA fragments) and application of a large body of spectroscopic and other physico-chemical techniques. Thanks to these efforts there is presently no other metal ion whose reactions with nucleic acids are better understood than Pt. In a series of chapters, basic studies on the interactions of Pt electrophiles with nucleobases, oligonucleotides, DNA, amino acids, peptides and proteins are reported, which use, among others, sophisticated NMR techniques or X-ray crystallography, to get remarkable understanding of details on such reactions. Reactivity of cisplatin, once bound to DNA and formerly believed to be inert enough to stay, is an emerging phenomenon. It has (not yet) widely been studied but is potentially extremely important. Medicinal bioinorganic chemistry - the role of metal compounds in medicine - has received an enormous boost from cisplatin, and so has bioinorganic chemistry as a whole. There is hardly a better example than cisplatin to demonstrate what bioinorganic chemistry is all about: The marriage between classic inorganic (coordination) chemistry and the other life sciences - medicine, pharmacy, biology, biochemistry. Cisplatin has left its mark also on areas that are generally considered largely inorganic. The subject of mixed-valance Pt compounds is an example: From the sleeping beauty it made its way to the headlines of scientific journals, thanks to a class of novel Pt antitumor agents, the so-called "platinum pyrimidine blues". In the aftermath diplatinum (III) compounds were recognized and studies in large numbers, and now an organometalic chemistry of these diplatinum (III) species is beginning to emerge. The final section of the book is concerned with new developments such as novel di- and trinuclear Pt(II) drugs with DNA binding properties different from those of cisplatin, with orally active Pt(IV) drugs which are presently in clinical studies, and with attempts to modify combinatorial chemistry in such a way that it may become applicable to fast screening of Pt antitumor drugs. The potential of including computational methods in solving questions of Pt-DNA interactions is critically dealt with in the concluding chapter.
Cancer is a dreadful disease and any practical solution in combating this disease is of paramount importance to public health. Cancer patients have burdened by drug induced toxic side effects, and no turned to seek help from the complementary and alternative medicine hoping for a better cure. Inorganic chemotherapy has been considerably boosted in recent years by the discovery and exploitation of Antitumor compounds based on platinum. Some Gold (III) complexes display similar chemistry. Pharmacological activity to cis-platin and its analogues are now the basis of multimillion dollars industry and bring benefit to thousands of cancer patients. Platinum based anticancer drugs induces normal tissue toxicity particularly to the kidneys and thus alternative metal compounds are presently being evaluated in clinical trials.
Book Synopsis Transition Metal Complexes as Anticancer Drugs in Pharma Industry by : Prakash Kinthada
Download or read book Transition Metal Complexes as Anticancer Drugs in Pharma Industry written by Prakash Kinthada and published by LAP Lambert Academic Publishing. This book was released on 2018-06-22 with total page 56 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cancer is a dreadful disease and any practical solution in combating this disease is of paramount importance to public health. Cancer patients have burdened by drug induced toxic side effects, and no turned to seek help from the complementary and alternative medicine hoping for a better cure. Inorganic chemotherapy has been considerably boosted in recent years by the discovery and exploitation of Antitumor compounds based on platinum. Some Gold (III) complexes display similar chemistry. Pharmacological activity to cis-platin and its analogues are now the basis of multimillion dollars industry and bring benefit to thousands of cancer patients. Platinum based anticancer drugs induces normal tissue toxicity particularly to the kidneys and thus alternative metal compounds are presently being evaluated in clinical trials.