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.
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.
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.
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.
Medicinal Chemistry of Anticancer Drugs, Second Edition, provides an updated treatment from the point of view of medicinal chemistry and drug design, focusing on the mechanism of action of antitumor drugs from the molecular level, and on the relationship between chemical structure and chemical and biochemical reactivity of antitumor agents. Antitumor chemotherapy is a very active field of research, and a huge amount of information on the topic is generated every year. Cytotoxic chemotherapy is gradually being supplemented by a new generation of drugs that recognize specific targets on the surface or inside cancer cells, and resistance to antitumor drugs continues to be investigated. While these therapies are in their infancy, they hold promise of more effective therapies with fewer side effects. Although many books are available that deal with clinical aspects of cancer chemotherapy, this book provides a sorely needed update from the point of view of medicinal chemistry and drug design. - Presents information in a clear and concise way using a large number of figures - Historical background provides insights on how the process of drug discovery in the anticancer field has evolved - Extensive references to primary literature
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.
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.
"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. "
