Dna Interactions With Inorganic Anticancer Drugs
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Author | : Stephen B. Howell |
Publisher | : Springer Science & Business Media |
Total Pages | : 563 |
Release | : 1991 |
Genre | : Medical |
ISBN | : 030644027X |
Taken together the data presented in this review, and work by many other investigators, support the notion that DNA excision repair is important in a tumor cell's resistance to platinum compounds. Inhibition of this repair system by combination chemotherapy with the excision repair inhibitors HU and Ara-C produces synergistic cell kills and increased levels and persistance of DNA interstrand crosslinks. The studies with cis-DDP and ~-DDP in combination with UV induced thymine dimers suggest that there may be competition for DNA repair enzymes between the dimer and the platinum lesion. Whether the competing lesion is an intrastrand crosslink, interstrand crosslink, or platinum monoadduct (or all of these lesions) cannot be determined. The similarity between an intrastrand crosslink and a cyclobutane dimer suggests that these lesions may compete for repair. However, the increased peak levels of interstrand crosslinks, and increased persistence of these lesions at later time points suggest that this lesion may also be a substrate for the repair system. These observations may be of clinical relevance. Recently Dr. Kathy Albain of our institution has completed a Phase III I study using a 12 hour pretreatment with HU and Ara-C in patients prior to their cis-DDP therapy. She observed a significant number of responders in this trial (54). She is currently completing a second Phase IIII study substituting IV HU for the oral formulation. We anticipate initiating other clinical trials based upon these observations.
Author | : Shahid Ul Islam |
Publisher | : John Wiley & Sons |
Total Pages | : 432 |
Release | : 2020-07-08 |
Genre | : Science |
ISBN | : 1119640423 |
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.
Author | : |
Publisher | : BoD – Books on Demand |
Total Pages | : 112 |
Release | : 2020-02-19 |
Genre | : Science |
ISBN | : 1789840473 |
Biophysical chemistry is one of the most interesting interdisciplinary research fields. Some of its different subjects have been intensively studied for decades. Now the field attracts not only scientists from chemistry, physics, and biology backgrounds but also those from medicine, pharmacy, and other sciences. We aimed to start this version of the book Biophysical Chemistry from advanced principles, as we include some of the most advanced subject matter, such as advanced topics in catalysis applications (first section) and therapeutic applications (second section). This led us to limit our selection to only chapters with high standards, therefore there are only six chapters, divided into two sections. We have assumed that the interested readers are familiar with the fundamentals of some advanced topics in mathematics such as integration, differentiation, and calculus and have some knowledge of organic and physical chemistry, biology, and pharmacy. We hope that the book will be valuable to graduate and postdoctoral students with the requisite background, and by some advanced researchers active in chemistry, biology, biochemistry, medicine, pharmacy, and other sciences.
Author | : Bernhard Lippert |
Publisher | : John Wiley & Sons |
Total Pages | : 630 |
Release | : 1999 |
Genre | : Medical |
ISBN | : 9783906390208 |
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.
Author | : Jonathan L. Sessler |
Publisher | : |
Total Pages | : 480 |
Release | : 2005 |
Genre | : Medical |
ISBN | : |
This book reviews the current diagnostic and therapeutic uses of metal-containing compounds in medicine, as well as the role of metals in disease.
Author | : Astrid Sigel |
Publisher | : Walter de Gruyter GmbH & Co KG |
Total Pages | : 588 |
Release | : 2018-02-05 |
Genre | : Science |
ISBN | : 311047073X |
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.
Author | : Ivano Bertini |
Publisher | : University Science Books |
Total Pages | : 794 |
Release | : 2007 |
Genre | : Science |
ISBN | : 9781891389436 |
Part A.: Overviews of biological inorganic chemistry : 1. Bioinorganic chemistry and the biogeochemical cycles -- 2. Metal ions and proteins: binding, stability, and folding -- 3. Special cofactors and metal clusters -- 4. Transport and storage of metal ions in biology -- 5. Biominerals and biomineralization -- 6. Metals in medicine. -- Part B.: Metal ion containing biological systems : 1. Metal ion transport and storage -- 2. Hydrolytic chemistry -- 3. Electron transfer, respiration, and photosynthesis -- 4. Oxygen metabolism -- 5. Hydrogen, carbon, and sulfur metabolism -- 6. Metalloenzymes with radical intermediates -- 7. Metal ion receptors and signaling. -- Cell biology, biochemistry, and evolution: Tutorial I. -- Fundamentals of coordination chemistry: Tutorial II.
Author | : Kenneth Kam-Wing Lo |
Publisher | : Academic Press |
Total Pages | : 408 |
Release | : 2016-12-30 |
Genre | : Science |
ISBN | : 012803887X |
Inorganic and Organometallic Transition Metal Complexes with Biological Molecules and Living Cells provides a complete overview of this important research area that is perfect for both newcomers and expert researchers in the field. Through concise chapters written and edited by esteemed experts, this book brings together a comprehensive treatment of the area previously only available through scattered, lengthy review articles in the literature. Advanced topics of research are covered, with particular focus on recent advances in the biological applications of transition metal complexes, including inorganic medicine, enzyme inhibitors, antiparasital agents, and biological imaging reagents. - Geared toward researchers and students who seek an introductory overview of the field, as well as researchers working in advanced areas - Focuses on the interactions of inorganic and organometallic transition metal complexes with biological molecules and live cells - Foscuses on the fundamentals and their potential therapeutic and diagnostic applications - Covers recent biological applications of transition metal complexes, such as anticancer drugs, enzyme inhibitors, bioconjugation agents, chemical biology tools, and bioimaging reagents
Author | : Nicholas V Hud |
Publisher | : Royal Society of Chemistry |
Total Pages | : 448 |
Release | : 2008-10-16 |
Genre | : Science |
ISBN | : 1847558763 |
Natural biochemical processes are routinely being discovered in living cells that involve RNA. Some of these processes, such as RNA interference, are now being exploited for biotechnology and medicinal applications. DNA has also proven in recent years to be more than a passive storehouse of information. For example, non-B-form DNA structures formed by G-rich DNA have been shown to participate in the regulation of gene expression, a discovery that presents new possibilities for drug targets in the genome. The current quest to understand how nucleic acid functions at the most fundamental level requires that we have a detailed understanding of nucleic acid-metal ion interactions. Because RNA and DNA are polyanions the structure and biological function of these biopolymers depends strongly on their association with metal ions. While this intimate connection between metal ions and nucleic function has been appreciated for decades, the noncovalent and dynamic nature of these interactions has continually presented challenges to the development of accurate and quantitative descriptions. Over the past few years the development of solution state spectroscopic techniques and the achievement of high resolution X-ray crystal structures have provided tremendous insights into the nature of nucleic acid-metal ion interactions, including direct evidence for their importance in determining nucleic acid structure, from the dictation of folding pathways followed by large RNA molecules to the subtle modulation of DNA groove widths. This new book provides a comprehensive review of the experimental studies that define our current understanding of nucleic acid-metal ion interactions with a particular emphasis being placed on experimental biophysical studies. However, the book is not merely a current review of the literature, as original material and fresh perspectives on published results are also presented. Particularly noteworthy topics include: -The chapter by Williams and fellow workers which reviews information provided by x-ray crystal structures and discusses what this information has revealed about the unique nature of Mg2+ interactions with RNA phosphate groups. The authors provide fresh insights, based upon structural comparisons, for how these interactions govern the local folding pathways of RNA. By dedicating separate chapters to the participation of metal ions in the kinetics and thermodynamics of RNA folding, this volume provides a more in depth treatise of both areas than is typically possible for reviews in which these two related, but distinct, topics are combined -Polyelectrolyte models of nucleic acids have proven to be extremely valuable for understanding the sequestering counterions in a so-called diffuse cloud around polymeric DNA. J. Michael Schurr provides a comprehensive review of polyanion models. Despite the success of polyelectrolyte models in describing some physical properties of nucleic acids, this topic is not always sufficiently understood by many researchers to make use of these models and this chapter serves as a valuable and up to date introduction to this topic. -The chapter by Pizarro and Sadler on metal ion-nucleic acid interactions in disease and medicine is complemented by a chapter by Lippert on coordinative bond formation between metal ions and nucleic acid bases. Together, these two chapters provide an overview of transition metal ion interactions with nucleic acids that illustrates the promise and peril that is associated with direct metal ion coordination to nucleic acid bases in living cells. The book is sufficiently detailed to serve as a reference source for researchers active in the field of nucleic acids biophysics and molecular biology. In addition, chapter authors have added introductory material and enough background material in each chapter so that the book can also can serve as an entry point for students and researchers that have not previously worked in the field which will make the book of lasting value and more accessible by a wider audience.
Author | : Loutfy H. Madkour |
Publisher | : Academic Press |
Total Pages | : 652 |
Release | : 2019-08-27 |
Genre | : Science |
ISBN | : 0128197781 |
Nucleic Acids as Gene Anticancer Drug Delivery Therapy highlights the most recent developments in cancer treatment using nucleic acids, nanoparticles and polymer nanoparticles for genomic nanocarriers as drug delivery, including promising opportunities for targeted and combination therapy. The development of a wide spectrum of nanoscale technologies is beginning to change the scientific landscape in terms of disease diagnosis, treatment, and prevention. This book presents the use of nanotechnology for medical applications, focusing on its use for anticancer drug delivery. Various intelligent drug delivery systems such as inorganic nanoparticles and polymer-based drug delivery are discussed. The use of smart drug delivery systems seems to be a promising approach for developing intelligent therapeutic systems for cancer immunotherapies and is discussed in detail along with nucleic acid-targeted drug delivery combination therapy for cancer. Nucleic Acids as Gene Anticancer Drug Delivery Therapy will be a useful reference for pharmaceutical scientists, pharmacologiests, and those involved in nanotechnology and cancer research. - Discusses intelligent drug delivery systems such as inorganic nanoparticles and polymer-based drug delivery - Contains a comprehensive comparison of various delivery systems, listing their advantages and limitations - Presents combination therapy as a new hope for enhancing current gene-based treatment efficacy