Download or read book Development of Non traditional Platinum Anticancer Agents written by Daniel E. Lee and published by . This book was released on 2015 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Platinum anticancer compounds with cis geometry, similar to cisplatin, have been explored to circumvent the cisplatin resistance; however, they were not considered broadly active in cisplatin cells due to exhibiting similar or same cell death mechanism as cisplatin. Platinum compounds with trans geometry were less studied due to transplatin being clinically inactive; but with few structural modifications, they resulted in unaffected cytotoxic activities in cisplatin resistant cells with structural modification by exhibiting different modes of DNA binding. This research focused on further exploring and establishing structure-activity relationship of two promising non-classical series of platinum compounds with trans-geometry: trans-platinum planar amine (TPA) compounds and noncovalently binding polynuclear platinum compounds (PPC-NC). During this research, further optimizations of the reactivity of TPA compounds were accomplished by modifying the leaving carboxylate groups. The effects of modified reactivity were probed by a systematic combination of chemical and biophysical assays, followed by evaluating their biological effects in cells. To establish the structural-activity relationship of PPC-NCs, Mono-, Di-, Tri-, and Tetraplatin NC with charge of 4+, 6+, 8+, and 10+ were synthesized and evaluated by utilizing biophysical and biological assays. Lastly, a new class of polynuclear platinum compounds, Hybrid-PPCs, were synthesized and evaluated to overcome the pharmacokinetic problems of BBR3464, phase II clinical trial anticancer drug developed previously in our laboratory.

Download or read book Investigation of Non traditional Platinum Anti tumor Agents written by Ralph Kipping and published by . This book was released on 2011 with total page 243 pages. Available in PDF, EPUB and Kindle. Book excerpt:

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 Developments in the Chemistry and Nanodelivery of Platinum Anticancer Agents written by Timothy Charles Johnstone and published by . This book was released on 2014 with total page 376 pages. Available in PDF, EPUB and Kindle. Book excerpt: Approximately half of all patients receiving cancer chemotherapy are treated with a platinum-containing drug. Despite this intense clinical use, only three platinum complexes, cisplatin, carboplatin, and oxaliplatin, are approved by the United States Food and Drug Administration for the treatment of cancer. A number of side effects accompany platinum-based therapy and novel approaches are under investigation to attenuate these negative effects and circumvent tumor resistance, be it inherent or acquired. One approach is to use non-classical platinum agents such as platinum(IV) prodrugs and monofunctional platinum(II) complexes. The latter, unlike the classical platinum drugs, can only form one bond to the biological target, DNA. Another strategy is to exploit the advantages offered by nanodelivery. The work presented here spans a range of topics aimed at furthering the development of platinum anticancer therapy along these lines. Fundamental platinum chemistry has been explored to provide ready access to platinum(II) starting materials such as oxaliplatin and mixed ammine/amine platinum(II) complexes. Novel platinum(IV) architectures were uncovered while investigating the oxidative halogenation of cisplatin and carboplatin. Nanoparticle constructs based on the biocompatible amphiphilic block copolymer, PLGA-PEG, have been devised that are capable of delivering both hydrophobic and hydrophilic platinum complexes. Nanoparticle encapsulation has a significant effect on the in vivo properties of the platinum(IV) prodrug mitaplatin. Fundamental studies of the chirality of a potent monofunctional complex, phenanthriplatin, revealed aspects of its interaction with derivatives of the nucleobase guanine, that may have a significant effect on the cellular processing of the DNA adducts formed by this compound. Finally, nanoparticle delivery was used to enhance the ability of phenanthriplatin and phenanthriplatin prodrugs to inhibit the growth of tumors in mice.

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 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.

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 Anticancer Agents Recently Developed in the People s Republic of China a Review written by Chen-Pien Li and published by . This book was released on 1973 with total page 272 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Anticancer Drug Development Guide written by Beverly A. Teicher and published by Springer Science & Business Media. This book was released on 2004-02-01 with total page 514 pages. Available in PDF, EPUB and Kindle. Book excerpt: This unique volume traces the critically important pathway by which a "molecule" becomes an "anticancer agent. " The recognition following World War I that the administration of toxic chemicals such as nitrogen mustards in a controlled manner could shrink malignant tumor masses for relatively substantial periods of time gave great impetus to the search for molecules that would be lethal to specific cancer cells. Weare still actively engaged in that search today. The question is how to discover these "anticancer" molecules. Anticancer Drug Development Guide: Preclinical Screening, Clinical Trials, and Approval, Second Edition describes the evolution to the present of preclinical screening methods. The National Cancer Institute's high-throughput, in vitro disease-specific screen with 60 or more human tumor cell lines is used to search for molecules with novel mechanisms of action or activity against specific phenotypes. The Human Tumor Colony-Forming Assay (HTCA) uses fresh tumor biopsies as sources of cells that more nearly resemble the human disease. There is no doubt that the greatest successes of traditional chemotherapy have been in the leukemias and lymphomas. Since the earliest widely used in vivo drug screening models were the murine L 1210 and P388 leukemias, the community came to assume that these murine tumor models were appropriate to the discovery of "antileukemia" agents, but that other tumor models would be needed to discover drugs active against solid tumors.

Download or read book Improving The Efficacy And Utility Of Platinum Based Anticancer Agents written by Payel Datta and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Since the discovery of cisplatin, the development of platinum-based chemotherapeutic drugs has transformed the treatment of multiple cancers. Lately, these account for almost half of all agents used in clinical chemotherapy 1. Despite their widespread use and initial effectiveness for specific cancers, several drawbacks exist which limit both the cure rate and the patient's survival. The drug's premature reduction in the blood stream, low tumor selectivity2, and drug resistance are some of the major downsides in the long-term usage of cisplatin; thus, finding ways to alleviate these drawbacks remains pivotal in the effective treatment of cancers. Herein, our work focuses on the development of platinum-based anticancer drugs that have less premature drug reduction, greater tumor selectivity, and overcome drug resistance by targeting the mitochondria of cancer cells. The first chapter of my dissertation describes the introduction and background of platinum based anticancer drugs. Synthesis, cell-based studies, and analysis of the following topics will be discussed in later chapters. I. Engineering liposomal nanoparticles of cholesterol-tethered amphiphilic Pt (IV) prodrugs with prolonged circulation time in blood In chapter two of my dissertation, we present a stabilized liposomal formulation of the platinum. anticancer drug. A cholesterol conjugated amphiphilic Pt (IV) prodrug of cisplatin is synthesized and encapsulated in liposomal formulation. This formulation shows marked resistance against premature reduction in human plasma and increased the half-life of Pt(IV) prodrug to over six times that of cisplatin. The paper has been published in 2020. II. Development of mitochondria targeting Pt (IV)- Ru (II) binuclear complex to treat ovarian cancer In chapter three of my dissertation, we present a novel design of Ru (bpy)2 conjugated fatty acid like Pt(IV) prodrug. This binuclear organometallic complex shows enhanced efficacy to treat ovarian cancer by targeting and damaging mitochondria, the powerhouse of cell. Manuscript is currently under preparation. III. Optimization of potency of Pt (IV) prodrugs via a small library of Pt (IV) derivatives Chapter four of my dissertation will be focused on the development and evaluation of a small library of fatty acid like Pt(IV) prodrug derivatives' efficacy. These prodrugs are designed to target mitochondria to eliminate resistant cancer cells. The modification of head groups using various functional group and varying the carbon chain length, a comparative analysis will be discussed based on cancerous cell damaging effectiveness. Manuscript is currently under preparation.

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.

Download or read book Novel Anticancer Agents written by Alex A. Adjei and published by Elsevier. This book was released on 2011-04-28 with total page 478 pages. Available in PDF, EPUB and Kindle. Book excerpt: Novel Anticancer Agents offers pertinent basic science information on strategies used for the rational design and discovery of novel anticancer agents, and, in addition, translational studies involving clinical trial design and execution with these novel, mostly cytostatic agents. This book covers basic science strategies that are being used in drug discovery and preclinical evaluation focused on novel molecular targets, as well as clinical trial methodology including clinical pharmacokinetics and imaging to address issues of efficacy evaluation of the new, relatively non-cytotoxic anticancer agents. At present, there is no book that provides such an integration of basic and clinical studies of novel anticancer agents, covering both drug discovery and translational research extensively. Addresses the critical issues involved in the development of novel agents for cancer therapy by experts in the field Presents drug discovery strategies Discusses regulatory issues surrounding drug development

Download or read book Methods of Development of New Anticancer Drugs written by National Cancer Institute (U.S.) and published by . This book was released on 1977 with total page 270 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Rethinking Platinum Anticancer Drug Design Towards Targeted and Immuno chemotherapeutic Approaches written by Daniel Yuan Qiang Wong and published by Springer. This book was released on 2018-06-18 with total page 169 pages. Available in PDF, EPUB and Kindle. Book excerpt: This thesis describes the authors’ pioneering efforts in the conceptualization and implementation of combined platinum-based immuno-chemotherapeutics, which represent a significant paradigm shift from the conventional approach of directly targeting cancer. The work described has opened up a rich and largely unexplored area for platinum-based drug design, and ultimately paves the way for superior immuno-chemotherapeutics with better clinical outcome for patients. Historically, the contribution of the immune system to chemotherapy outcomes has been neglected, as anticancer drugs were believed to be immunosuppressive. However, this has been challenged by contemporary evidence suggesting that many chemotherapeutics, including platinum-based agents, stimulate the innate and/or adaptive immune system and that these “secret allies” contribute tangibly to clinical outcomes. A multi-pronged immuno-chemotherapeutic approach not only shrinks tumors, but more importantly, reactivate dormant immune responses to malignancies, eliminating residual cancer cells.

Download or read book New Approaches to Natural Anticancer Drugs written by Soodabeh Saeidnia and published by Springer. This book was released on 2015-02-05 with total page 117 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides an up-to-date review of recently identified natural anti-tumor compounds from various natural origins including plants, fungi, endophytic fungi and marine organisms. It also includes discussion of new areas such as biotechnology and nanoparticles. Chapters explain the challenges and developments in anti-cancer drug discovery approaches, traditional remedies for prevention and treatment of cancer, marine-derived anti-cancer compounds, and antibiotics used as anti-cancer agents, as well as different classes of terpenoids and carbohydrates, which have been the subject of discussion in this field as efficient anti-cancer candidates. This book will be a concise guide for researchers in the field of pharmaceutical sciences, students and residents in pharmacy and medicine as well as those researching phytochemistry and natural products.

Download or read book Advances in Anticancer Agents in Medicinal Chemistry written by Michelle Prudhomme and published by Bentham Science Publishers. This book was released on 2013-06-14 with total page 495 pages. Available in PDF, EPUB and Kindle. Book excerpt: Advances in Anticancer Agents in Medicinal Chemistry is an exciting eBook series comprising a selection of updated articles previously published in the peer-reviewed journal Anti-Cancer Agents in Medicinal Chemistry. The second Volume of this eBook series gathers updated reviews on several classes of molecules exhibiting anticarcinogenic potential as well as some important targets for the development of novel anticancer drugs.

Download or read book Novel Strategies for Improving the Pharmacological Properties of Platinum acridine Anticancer Agents written by Song Ding and published by . This book was released on 2015 with total page 543 pages. Available in PDF, EPUB and Kindle. Book excerpt: Unlike traditional cisplatin-type platinum-based anticancer drugs, platinum-acridine hybrid agents were designed as dual platinating/intercalating DNA-targeted cytotoxics, which are able to cause cancer cell death at low-nanomolar concentrations. Unfortunately, the preclinical development of these agents has been hampered by their severe systemic toxicity. The goal of this dissertation was to devise strategies that improve the drug-like properties of platinum-acridines and allow their safe delivery. To achieve this, several classical and newly developed synthetic methodologies have been used to generate functionally unique hybrid agents. Several model systems, whole-cell assays, and animal studies have been used in this dissertation to validate their design and demonstrate their utility as anticancer agents. A modular screening platform was developed, based on a platinum-mediated amine-to-nitrile addition reaction, for rapid identification of functionalized platinum-acridine agents. These pre-screening assays produced functionalized "warheads" while providing insight into structure–activity relationships (SAR). Using several library members, we set out to explore synthetic approaches to construct platinum-acridine-based conjugates. A chemically robust azide-modified platinum-acridine was selected to validate the feasibility of copper-mediated and copper-free click chemistry as platinum-compatible conjugation reactions. This chemistry was used to attach fluorescent molecules to detect platinum-acridines in cancer cells by confocal microscopy. Both fluorophore tagging prior to incubation with cells and post-labeling methods were explored. In addition, a hydroxyl-modified warhead was conjugated with endoxifen via a chemically stable carbamate bond to produce a highly active hybrid agent in estrogen receptor positive (ER+) breast cancer. In another study, lipophilic ester-based prodrugs of platinum–acridines were generated showing improved drug-like properties (e. g., partition coefficients, logD). Two distinct pathways by which the target compounds can be activated have been confirmed by LC-ESMS and/or NMR techniques: (i) a platinum-assisted, self-immolative ester cleavage in a low-chloride environment, and (ii) enzymatic cleavage by human carboxylesterase-2 (hCES-2). Highly efficient amide coupling reactions in platinum complexes were also developed. This modular approach can be used to assemble a diverse library of platinum-acridines containing other bioactive components, such as molecularly targeted therapies, targeted ligands, and chemosensitizers. Finally, liposomal encapsulation of platinum-acridine was achieved, and the formulations were evaluated in A549 lung cancer xenograft models in mice. Improved anticancer efficacy of one of the liposomal formulations compared with the free drug was observed in this assay. In conclusion, the research in this dissertation has laid the foundation for the future preclinical development of platinum-acridines as oncology drugs by devising new synthetic methodology and providing proof-of-concept data in clinically relevant models of cancer.