Metal Based Anticancer Agents

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.

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.

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 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.

Working from basic chemical principles, Metals in Medicine 2nd Edition describes a wide range of metal-based agents for treating and diagnosing disease. Thoroughly revised and restructured to reflect significant research activity and advances, this new edition contains extensive updates and new pedagogical features while retaining the popular feature boxes and end-of-chapter problems of the first edition. Topics include: Metallo-Drugs and their action Platinum drugs for treating cancer Anticancer agents beyond cisplatin including ruthenium, gold, titanium and gallium Responsive Metal Complexes Treating arthritis and diabetes with metal complexes Metal complexes for killing bacteria, parasites and viruses Metal ion imbalance and its links to diseases including Alzheimer’s, Wilson’s and Menkes disease Metal complexes for detecting disease Nanotechnology in medicine Now in full colour, Metals in Medicine 2nd Edition employs real-life applications and chapter-end summaries alongside feature boxes and problems. It provides a complete and methodical examination of the use of metal complexes in medicine for advanced undergraduate and postgraduate students in medicinal inorganic chemistry, bioinorganic chemistry, biochemistry, pharmacology, biophysics, biology and bioengineering. It is also an invaluable resource for academic researchers and industrial scientists in inorganic chemistry, medicinal chemistry and drug development.

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.

"Volume 35 covers the biological cycling of iron in oceans; the transport of iron in microorganisms, fungi, and plants; the roles and properties of siderophores; the regulation of iron transport and uptake in animals, plants, and microorganisms, and more. "

When this book was first conceived as a project the expanding interest in the clinical use of platinum and gold complexes made a survey of the relevant biological properties of metal complexes timely and appropriate. This timeliness has not diminished during the gestation and final publica tion of the manuscript. The introduction contains an explanation of the layout and approach to the book, which I wrote as an overall survey of the wide variety of biological properties of metal complexes. Hopefully, the reader will see the parallels in mechanisms and behavior, even in different organisms. The writing was considerably helped by the enthusiasm and confidence (totally unearned on my part) in the project of Professor Brian James and lowe him my special thanks. I also owe a great debt of gratitude to my colleagues, and especially to Eucler Paniago, of the Universidade Federal de Minas Gerais, for their comprehension and for the initial leave of absence which allowed me to begin the project. To those who read some or all of the manuscript and made suggestions, Bernhard Lippert, Kirsten Skov, and Tom Tritton, as well as the editor's reviewer I am also grateful. As usual, the final responsibility for errors or otherwise rests with the author.