Download or read book Interaction of Potential Antitumor Drugs of Platinum II with Nucleic Acids written by Joycette Santos Santori and published by . This book was released on 1992 with total page 194 pages. Available in PDF, EPUB and Kindle. Book excerpt:
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.
Download or read book Platinum Coordination Complexes in Cancer Chemotherapy written by T.A. Connors and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 232 pages. Available in PDF, EPUB and Kindle. Book excerpt: It was a great pleasure and honour to have been invited to attend this Seminar and to present a final impression. The association in this field between the Chester Beatty Research Institute and Dr. Rosenberg's School at East Lansing is something which I specially value and many would doubtless like to know how it came about. In the course of its work in carcinogenesis and on chemotherapy over many years, the Chester Beatty Research Institute was frequently drawn to the importance of many metals - as for example lead, iron, metalloid arsenic and the metalloid quali ties of the carcinogenic hydrocarbons. Interest started in platinum many years ago, following the possibility, c1aimed by others, that various complexes between the metal and mercaptopurine might possess significant chemotherapeutic properties. Va rious attempts to confirm such findings ended, however, in complete failure. Interest in platinum was revived by the fresh observations of Dr. Rosenberg and his collea gues, and here the outcome was entirely different. Very soon it was possible to con firm the intense growth-inhibitory properties of cis-platinum (II) diamminedi chloride and related substances. After communicating these results to Dr. Rosenberg, it was a pleasure to welcome hirn in London where he gave a Seminar which greatly engaged the interest of many of the staff. Later, several of these were to enjoy Dr. Rosenberg's hospitality at an international conference on the subject to be held in East Lansing, where many rapidly developing aspects were open for discussion.
Download or read book Platinum Based Drugs in Cancer Therapy written by Lloyd R. Kelland and published by Springer Science & Business Media. This book was released on 2000-03-24 with total page 340 pages. Available in PDF, EPUB and Kindle. Book excerpt: Leading international experts comprehensively review all aspects of platinum anticancer drugs and their current use in treatment, as well as examining their future therapeutic prospects. Writing from a variety of disciplines, these authorities discuss the chemistry of cisplatin in aqueous solution, the molecular interaction of platinum drugs with DNA, and such exciting new areas as DNA mismatch repair and replicative bypass, apoptosis, and the transport of platinum drugs into tumor cells. The emergent platinum drugs of the future-orally active agents, the sterically hindered ZD0473, and the polynuclear charged platinum BBR3464-are also fully considered. Timely and interdisciplinary, Platinum-Based Drugs in Cancer Therapy offers cancer therapeutics specialists an illuminating survey of every aspect of platinum drugs from mechanisms of action to toxicology, tumor resistance, and new analogs.
Download or read book Interaction of antitumor platinum compounds with nucleic acid f written by Antonius Theodorous Maria Marcelis and published by . This book was released on 19?? with total page 118 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Interaction of Antitumor Platinum Compounds with Nucleic Acid Fragments written by Antonius T. Marcelis and published by . This book was released on 1982 with total page 105 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Holland Frei Cancer Medicine written by Robert C. Bast, Jr. and published by John Wiley & Sons. This book was released on 2017-03-10 with total page 2004 pages. Available in PDF, EPUB and Kindle. Book excerpt: Holland-Frei Cancer Medicine, Ninth Edition, offers a balanced view of the most current knowledge of cancer science and clinical oncology practice. This all-new edition is the consummate reference source for medical oncologists, radiation oncologists, internists, surgical oncologists, and others who treat cancer patients. A translational perspective throughout, integrating cancer biology with cancer management providing an in depth understanding of the disease An emphasis on multidisciplinary, research-driven patient care to improve outcomes and optimal use of all appropriate therapies Cutting-edge coverage of personalized cancer care, including molecular diagnostics and therapeutics Concise, readable, clinically relevant text with algorithms, guidelines and insight into the use of both conventional and novel drugs Includes free access to the Wiley Digital Edition providing search across the book, the full reference list with web links, illustrations and photographs, and post-publication updates
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.
Download or read book Structural and Functional Consequences of Platinum Anticancer Drug Binding to Free and Nucleosomal DNA written by Ryan Christopher Todd and published by . This book was released on 2010 with total page 229 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cisplatin, carboplatin, and oxaliplatin are three FDA-approved members of the platinum anticancer drug family. These compounds induce apoptosis in tumor cells by binding to nuclear DNA, forming a variety of adducts, and triggering cellular responses, one of which is the inhibition of transcription. The focus of this thesis is on studying the structure of these adducts, and correlating these effects with inhibition of transcription. Chapter 1 presents (i) a detailed review of the structural investigations of various Pt-DNA adducts and the effects of these lesions on global DNA geometry; (ii) research detailing inhibition of cellular transcription by Pt-DNA adducts; and (iii) a mechanistic analysis of how DNA structural distortions induced by platinum damage may inhibit RNA synthesis in vivo. These hypotheses will be explored in subsequent chapters of the thesis. In Chapter 2, features of the 2.17 A resolution X-ray crystal structure of cisdiammine(pyridine)chloroplatinum(II) (cDPCP) bound in a monofunctional manner to deoxyguanosine in a DNA duplex are discussed and compared to those of a cisplatin-1,2- d(GpG) intrastrand cross-link in double-stranded DNA. The global geometry of cDPCPdamaged DNA is quite different from that of DNA containing a cisplatin 1,2-d(GpG) cross-link. The latter platinated duplex is bent by ~40* toward the major groove at the site of the adduct; however, the monofunctional Pt-dG lesion causes no significant bending of the double helix. Like the cisplatin intrastrand adduct, however, the cDPCP moiety creates a distorted base pair step to the 5' side of the platinum site that may be correlated to its ability to destroy cancer cells. Structural features of monofunctional platinum adducts are analyzed, the results of which suggest that such adducts may provide a new platform for the design and synthesis of Pt anticancer drug candidates. The role of carbonate in the binding of cis-diamminedichloroplatinum(II) to DNA was investigated in Chapter 3 in order to understand the potential involvement of carbonato-cisplatin species in the mechanism of action of platinum anticancer agents. Cisplatin was allowed to react with single-stranded DNA in carbonate, phosphate, and HEPES buffers, and the products were analyzed by enzymatic digestion/mass spectrometry. The data from these experiments demonstrate (1) that carbonate, like other biological nucleophiles, forms relatively inert complexes with platinum that inactivate cisplatin, and (2) that the major cisplatin-DNA adduct formed is a bifunctional cross-link. These results are in accord with previous studies of cisplatin- DNA binding and reveal that the presence of carbonate has no consequence on the nature of the resulting adducts. The 1.77-A resolution X-ray crystal structure of a dodecamer DNA duplex with the sequence 5'-CCTCTGGTCTCC-3' that has been modified to contain a single engineered 1,2-cis- {Pt(NH 3)2}2+-d(GpG) cross-link, the major DNA adduct of cisplatin, is reported in Chapter 4. These data represent a significant improvement in resolution over the previously published 2.6-A structure. The ammine ligands in this structure are clearly resolved, leading to improved visualization of the cross-link geometry with respect to both the platinum center and to the nucleobases, which adopt a higher energy conformation. Also better resolved are the deoxyribose sugar puckers, which allow us to re-examine the global structure of platinum-modified DNA. Another new feature of this model is the location of four octahedral [Mg(H 20)6]2+ ion associated with bases in the DNA major groove and the identification of 124 ordered water molecules that participate in hydrogen bonding interactions with either the nucleic acid or the diammineplatinum(II) moiety. Chapter 5 discusses structural investigations of nucleosomal DNA modified by sitespecific platinum adducts. Nucleosome core particles containing a single 1,3-cis-{Pt(NH 3)2}2+_ d(GpTpG) intrastrand cross-link were synthesized and crystallized, and the X-ray structure was determined at 3.2 A resolution. The cisplatin adduct adopts a conformation facing toward the octamer core, in agreement with previous experiments. DNA in the vicinity of the Pt adduct has a similar helical bend as that observed in the NMR solution structure of free DNA containing the same cross-link, indicating that the rotational positioning power of cisplatin intrastrand crosslinks stems from the propensity to align the bent Pt-DNA structure with the DNA curvature arising from the nucleosome superhelix. Functional consequences of cisplatin binding to nucleosomal DNA are explored in Chapter 6. The effect of a single engineered platinum intrastrand cross-link on ATPindependent nucleosome mobility was investigated in vitro. Both 1,2-d(GpG) and 1,3-d(GpTpG) adducts of cisplatin inhibit translocation of DNA along the histone octamer, with the former Pt lesion providing a larger barrier. In vitro transcription assays with T7 RNA polymerase were conducted to determine whether cisplatin-DNA cross-links inhibit RNA synthesis by preventing access to nucleosomal DNA. Immobilized transcription templates containing a T7 RNAP promoter site, a single engineered cisplatin 1,2-d(GpG) or 1,3-d(GpTpG) intrastrand cross-link, and a phased nucleosome core particle were prepared. Analysis of resulting RNA transcript length revealed that the T7 RNAP elongation complex can overcome the energy barrier to nucleosome sliding caused by platinum intrastrand cross-links, but stalls when it reaches a Pt- DNA adduct placed on the DNA template strand. These results provide further evidence that intrastrand cross-links of cisplatin inhibit transcription by creating a physical barrier that the polymerase cannot pass. Appendices A and B summarize incomplete work that may be of use to future researchers working in this area. Appendix A describes attempts to isolate isomerically pure Pt- DNA probes containing a photoreactive benzophenone moiety, for use in cross-linking experiments that identify proteins that recognize and interact with cisplatin-DNA damage. In Appendix B efforts to obtain an X-ray crystal structure of an 1 Imer duplex DNA containing the 1,3- cis-{Pt(NH 3)2} 2 -d(GpTpG) intrastrand cross-link are reported. Appendix C details HPLC and mass spectrometric methods for purification and analysis of platinated oligonucleotides that were developed in the course of this research.
Download or read book Medicinal Chemistry of Anticancer Drugs written by Carmen Avendaño and published by Elsevier. This book was released on 2015-06-11 with total page 767 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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
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.
Download or read book Ruthenium and Other Non Platinum Metal Complexes in Cancer Chemotherapy written by Etienne Baulieu and published by Springer Science & Business Media. This book was released on 2013-03-07 with total page 228 pages. Available in PDF, EPUB and Kindle. Book excerpt: With contributions by numerous experts
Download or read book Synthesis of Best Seller Drugs written by Ruben Vardanyan and published by Academic Press. This book was released on 2016-01-07 with total page 870 pages. Available in PDF, EPUB and Kindle. Book excerpt: Synthesis of Best-Seller Drugs is a key reference guide for all those involved with the design, development, and use of the best-selling drugs. Designed for ease of use, this book provides detailed information on the most popular drugs, using a practical layout arranged according to drug type. Each chapter reviews the main drugs in each of nearly 40 key therapeutic areas, also examining their classification, novel structural features, models of action, and synthesis. Of high interest to all those who work in the captivating areas of biologically active compounds and medicinal drug synthesis, in particular medicinal chemists, biochemists, and pharmacologists, the book aims to support current research efforts, while also encouraging future developments in this important field. Describes methods of synthesis, bioactivity and related drugs in key therapeutic areas Reviews the main drugs in each of nearly 40 key therapeutic areas, also examining their classification, novel structural features, models of action, and more Presents a practical layout designed for use as a quick reference tool by those working in drug design, development and implementation
Download or read book Anticancer Drug Development written by Bruce C. Baguley and published by Elsevier. This book was released on 2001-11-17 with total page 411 pages. Available in PDF, EPUB and Kindle. Book excerpt: Here in a single source is a complete spectrum of ideas on the development of new anticancer drugs. Containing concise reviews of multidisciplinary fields of research, this book offers a wealth of ideas on current and future molecular targets for drug design, including signal transduction, the cell division cycle, and programmed cell death. Detailed descriptions of sources for new drugs and methods for testing and clinical trial design are also provided. One work that can be consulted for all aspects of anticancer drug development Concise reviews of research fields, combined with practical scientific detail, written by internationally respected experts A wealth of ideas on current and future molecular targets for drug design, including signal transduction, the cell division cycle, and programmed cell death Detailed descriptions of the sources of new anticancer drugs, including combinatorial chemistry, phage display, and natural products Discussion of how new drugs can be tested in preclinical systems, including the latest technology of robotic assay systems, cell culture, and experimental animal techniques Hundreds of references that allow the reader to access relevant scientific and medical literature Clear illustrations, some in color, that provide both understanding of the field and material for teaching
Download or read book Dosage Form Design Considerations written by and published by Academic Press. This book was released on 2018-07-28 with total page 881 pages. Available in PDF, EPUB and Kindle. Book excerpt: Dosage Form Design Parameters, Volume I, examines the history and current state of the field within the pharmaceutical sciences, presenting key developments. Content includes drug development issues, the scale up of formulations, regulatory issues, intellectual property, solid state properties and polymorphism. Written by experts in the field, this volume in the Advances in Pharmaceutical Product Development and Research series deepens our understanding of dosage form design parameters. Chapters delve into a particular aspect of this fundamental field, covering principles, methodologies and the technologies employed by pharmaceutical scientists. In addition, the book contains a comprehensive examination suitable for researchers and advanced students working in pharmaceuticals, cosmetics, biotechnology and related industries. Examines the history and recent developments in drug dosage forms for pharmaceutical sciences Focuses on physicochemical aspects, prefomulation solid state properties and polymorphism Contains extensive references for further discovery and learning that are appropriate for advanced undergraduates, graduate students and those interested in drug dosage design
Download or read book Biological Inorganic Chemistry written by Ivano Bertini and published by University Science Books. This book was released on 2007 with total page 794 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Chemosensitivity written by Rosalyn D. Blumenthal and published by Humana Press. This book was released on 2005-02-14 with total page 442 pages. Available in PDF, EPUB and Kindle. Book excerpt: A state-of-the art collection of readily reproducible laboratory methods for assessing chemosensitivity in vitro and in vivo, and for assessing the parameters that modulate chemosensitivity in individual tumors. Chemosensitivity,Volume 2: In Vivo Models, Imaging, and Molecular Regulators contains cutting-edge protocols for classifying tumors into response categories and for customizing therapy to individuals. These readily reproducible techniques allow measurements of DNA damage, apoptotic cell death, and the molecular and cellular regulators of cytotoxicity, as well as in vivo animal modeling of chemosensitivity. A companion volume, Volume 1: In Vitro Assays contains in vitro and in vivo techniques to identify which new agents or combination of agents are effective for each type of tumor.
