Developments in the Chemistry and Nanodelivery of Platinum Anticancer Agents

Developments in the Chemistry and Nanodelivery of Platinum Anticancer Agents PDF Author: Timothy Charles Johnstone
Publisher:
ISBN:
Category :
Languages : en
Pages : 376

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Book Description
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.

Platinum and Other Heavy Metal Compounds in Cancer Chemotherapy

Platinum and Other Heavy Metal Compounds in Cancer Chemotherapy PDF Author: Andrea Bonetti
Publisher: Springer Science & Business Media
ISBN: 1603274596
Category : Medical
Languages : en
Pages : 381

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Book Description
Cisplatin, the first member of the family of platinum-containing chemotherapeutic agents, was discovered by Barnett Rosenberg in 1965 and approved by the FDA for marketing in 1978. After 30 years of use in the clinic, cisplatin remains a central element of many treatment regimens. Cisplatin is still an irreplaceable component of a regimen that produces high cure rates in even advanced nonseminomatous germ-cell cancers, and is widely used in the treatment of ovarian cancers and other gynecologic cancers, head and neck, and numerous other tumor types. The development of carboplatin has reduced some of the adverse events associated with cisplatin treatment, and the introduction of the DACH platinum compound oxaliplatin has broadened the spectrum of activity of the platinums to include gastro-intestinal cancers, especially colorectal cancer. The clinical importance of this family of drugs continues to drive investigation into how these drugs work and how to improve their efficacy and reduce their toxicity. The papers in this volume were presented in Verona, Italy, during the tenth International Symposium on Platinum Coordination Compounds in Cancer Chemotherapy. The symposium was jointly organized by the Department of Oncology of the Mater Salutis Hospital – Azienda Sanitaria Locale 21 of the Veneto Region – and by the Department of Medicine and Public Health, Section of Pharmacology, the University of Verona. They reflect the vitality of this field and the increasing use of new molecular and cell biologic, genetic, and biochemical tools to identify approaches to further improve their use.

Platinum-Based Drugs in Cancer Therapy

Platinum-Based Drugs in Cancer Therapy PDF Author: Lloyd R. Kelland
Publisher: Springer Science & Business Media
ISBN: 1592590128
Category : Medical
Languages : en
Pages : 340

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Book Description
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.

Cisplatin

Cisplatin PDF Author: Bernhard Lippert
Publisher: John Wiley & Sons
ISBN: 9783906390208
Category : Medical
Languages : en
Pages : 628

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Book Description
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.

Gold and its Complexes in Anticancer Chemotherapy

Gold and its Complexes in Anticancer Chemotherapy PDF Author: Mohmmad Younus Wani
Publisher: Springer Nature
ISBN: 9813363142
Category : Medical
Languages : en
Pages : 173

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Book Description
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.

Nanopharmaceuticals: Principles and Applications Vol. 3

Nanopharmaceuticals: Principles and Applications Vol. 3 PDF Author: Vinod Kumar Yata
Publisher: Springer Nature
ISBN: 3030471209
Category : Technology & Engineering
Languages : en
Pages : 340

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Book Description
This book is the third volume on this subject and focuses on the recent advances of nanopharmaceuticals in cancer, dental, dermal and drug delivery applications and presents their safety, toxicity and therapeutic efficacy. The book also includes the transport phenomenon of nanomaterials and important pathways for drug delivery applications. It goes on to explain the toxicity of nanoparticles to different physiological systems and methods used to assess this for different organ systems using examples of in vivo systems.

Colon Cancer Diagnosis and Therapy

Colon Cancer Diagnosis and Therapy PDF Author: Naveen Kumar Vishvakarma
Publisher: Springer Nature
ISBN: 3030646688
Category : Medical
Languages : en
Pages : 453

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Book Description
Colorectal cancer (CRC) is a major global health challenge as the third leading cause for cancer related mortalities worldwide. Despite advances in therapeutic strategies, the five-year survival rate for CRC patients has remained the same over time due to the fact that patients are often diagnosed in advanced metastatic stages. Drug resistance is another common reason for poor prognosis. Researchers are now developing advanced therapeutic strategies such as immunotherapy, targeted therapy, and combination nanotechnology for drug delivery. In addition, the identification of new biomarkers will potentiate early stage diagnosis. This book is the second of three volumes on recent developments in colorectal diagnosis and therapy. Each volume can be read on its own, or together. Each volume focuses on different novel therapeutic advances, biomarkers, and identifies therapeutic targets for treatment. Written by leading international experts in the field, coverage addresses the role of diet habits and lifestyle in reducing gastrointestinal disorders and incidence of CRC. Chapters discuss current and future diagnostic and therapeutic options for colorectal cancer patients, focusing on immunotherapeutics, nanomedicine, biomarkers, and dietary factors for the effective management of colon cancer.

Bioinorganic Medicinal Chemistry

Bioinorganic Medicinal Chemistry PDF Author: Enzo Alessio
Publisher: John Wiley & Sons
ISBN: 352763312X
Category : Science
Languages : en
Pages : 625

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Book Description
This book gives a comprehensive overview about medicinal inorganic chemistry. Topics like targeting strategies, mechanism of action, Pt-based antitumor drugs, radiopharmaceuticals are covered in detail and offer the reader an in-depth overview about this important topic.

Chemical Epigenetics

Chemical Epigenetics PDF Author: Antonello Mai
Publisher: Springer Nature
ISBN: 3030429822
Category : Science
Languages : en
Pages : 569

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Book Description
This book presents an authoritative review of the most significant findings about all the epigenetic targets (writers, readers, and erasers) and their implication in physiology and pathology. The book also covers the design, synthesis and biological validation of epigenetic chemical modulators, which can be useful as novel chemotherapeutic agents. Particular attention is given to the chemical mechanisms of action of these molecules and to the drug discovery prose which allows their identification. This book will appeal to students who want to know the extensive progresses made by epigenetics (targets and modulators) in the last years from the beginning, and to specialized scientists who need an instrument to quickly search and check historical and/or updated notices about epigenetics.

Cisplatin, Current Status and New Developments

Cisplatin, Current Status and New Developments PDF Author: Archie W. Prestayko
Publisher:
ISBN:
Category : Medical
Languages : en
Pages : 552

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Book Description