Mechanisms of Accumulation and Biological Consequences of Polynuclear Platinum Compounds PDF Download
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Author: Peyman Kabolizadeh
Publisher:
ISBN:
Category : Antineoplastic agents
Languages : en
Pages : 444
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Book Description
The novel trinuclear complex, BBR3464 has undergone Phase II clinical trials and been shown to have greater cytotoxicity and cellular uptake than clinical anticancer platinum drugs such as cisplatin, oxaliplatin and carboplatin. The clinical efficacy of cisplatin, oxaliplatin and carboplatin is limited due to acquired resistance and dose limiting side effects. The three major pharmacological factors contributing to the intrinsic cytotoxicity of, and cellular resistance to, platinum drugs are (i) cellular uptake and efflux of platinum; (ii) the frequency and nature of Pt-DNA adducts; and (iii) deactivating metabolic reactions with sulfur-containing nucleophiles. Since decreased cellular uptake of platinum drugs is a common feature of resistant cells, investigating mechanisms of cellular uptake and efflux is of a great importance in the field of cancer biology. The mechanisms of uptake of Platinum drugs are diverse and complex. Similar to cisplatin, BBR3464 v as shown to use copper transporter hCTR1 and ATP7B for influx and efflux respectively. Organic cation transporters (OCT) did not play an important role in BBR3464 cellular uptake, however, desipramine, an OCT inhibitor had synergistic effects on platinun drugs-induced cytotoxicity. This effect is of high clinical relevance since desipramine, an antidepressant, is being used in prostate cancer patients for the treatment of neuropathic pain. The mechanism of this interaction was further addressed. Due to the high charge of BBR3464, studies have shown that its DNA binding has a non-covalent component. To examine the non covalent component, labile chloride leaving groups were replaced by non labile ammonia groups. Besides having higher cellular accumulation than BBR3464, the non covalent analogue, AH78, had a different mechanism of action in cells and showed promising results in vivo. These data confirm the validity of searching for new chemotypes outside the cisplatin structural class to aid in the treatment of recurrent, cisplatin-resistant cancers.
Author: Peyman Kabolizadeh
Publisher:
ISBN:
Category : Antineoplastic agents
Languages : en
Pages : 444
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Book Description
The novel trinuclear complex, BBR3464 has undergone Phase II clinical trials and been shown to have greater cytotoxicity and cellular uptake than clinical anticancer platinum drugs such as cisplatin, oxaliplatin and carboplatin. The clinical efficacy of cisplatin, oxaliplatin and carboplatin is limited due to acquired resistance and dose limiting side effects. The three major pharmacological factors contributing to the intrinsic cytotoxicity of, and cellular resistance to, platinum drugs are (i) cellular uptake and efflux of platinum; (ii) the frequency and nature of Pt-DNA adducts; and (iii) deactivating metabolic reactions with sulfur-containing nucleophiles. Since decreased cellular uptake of platinum drugs is a common feature of resistant cells, investigating mechanisms of cellular uptake and efflux is of a great importance in the field of cancer biology. The mechanisms of uptake of Platinum drugs are diverse and complex. Similar to cisplatin, BBR3464 v as shown to use copper transporter hCTR1 and ATP7B for influx and efflux respectively. Organic cation transporters (OCT) did not play an important role in BBR3464 cellular uptake, however, desipramine, an OCT inhibitor had synergistic effects on platinun drugs-induced cytotoxicity. This effect is of high clinical relevance since desipramine, an antidepressant, is being used in prostate cancer patients for the treatment of neuropathic pain. The mechanism of this interaction was further addressed. Due to the high charge of BBR3464, studies have shown that its DNA binding has a non-covalent component. To examine the non covalent component, labile chloride leaving groups were replaced by non labile ammonia groups. Besides having higher cellular accumulation than BBR3464, the non covalent analogue, AH78, had a different mechanism of action in cells and showed promising results in vivo. These data confirm the validity of searching for new chemotypes outside the cisplatin structural class to aid in the treatment of recurrent, cisplatin-resistant cancers.
Author:
Publisher:
ISBN:
Category : Dissertations, Academic
Languages : en
Pages : 902
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Book Description
Author: Astrid Sigel
Publisher: Walter de Gruyter GmbH & Co KG
ISBN: 311047073X
Category : Science
Languages : en
Pages : 588
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Book Description
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:
Publisher: ScholarlyEditions
ISBN: 1481691848
Category : Medical
Languages : en
Pages : 47
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Book Description
Proteoglycans—Advances in Research and Application: 2013 Edition is a ScholarlyPaper™ that delivers timely, authoritative, and intensively focused information about ZZZAdditional Research in a compact format. The editors have built Proteoglycans—Advances in Research and Application: 2013 Edition on the vast information databases of ScholarlyNews.™ You can expect the information about ZZZAdditional Research in this book to be deeper than what you can access anywhere else, as well as consistently reliable, authoritative, informed, and relevant. The content of Proteoglycans—Advances in Research and Application: 2013 Edition has been produced by the world’s leading scientists, engineers, analysts, research institutions, and companies. All of the content is from peer-reviewed sources, and all of it is written, assembled, and edited by the editors at ScholarlyEditions™ and available exclusively from us. You now have a source you can cite with authority, confidence, and credibility. More information is available at http://www.ScholarlyEditions.com/.
Author: Lloyd R. Kelland
Publisher: Springer Science & Business Media
ISBN:
Category : Medical
Languages : en
Pages : 370
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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.
Author:
Publisher: Academic Press
ISBN: 0128144246
Category : Medical
Languages : en
Pages : 881
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Book Description
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
Author:
Publisher:
ISBN:
Category : Medicine
Languages : en
Pages : 1840
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Book Description
Author: Patrick M. Woster
Publisher: Royal Society of Chemistry
ISBN: 184973190X
Category : Medical
Languages : en
Pages : 303
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Book Description
This is the first comprehensive description of the discovery and therapeutic potential of polyamine drugs.
Author: Shahid Ul-Islam
Publisher: John Wiley & Sons
ISBN: 1119640423
Category : Science
Languages : en
Pages : 432
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Book Description
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: Russell N. Grimes
Publisher: Academic Press
ISBN: 0128019050
Category : Science
Languages : en
Pages : 1060
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Book Description
Carboranes, Third Edition, by Russell Grimes, is the definitive resource on the subject. Completely updated with a wealth of research and review articles published in this active field since the previous volume was released in 2011, the book provides a readable and concise introduction to the basic principles underlying the synthesis, structures, and reactions of carboranes, heterocarboranes, and metallacarboranes. Following the valuable foundational information, the book explores the advances in practical applications for the many areas in which experts have discovered that carboranes afford new possibilities for solving problems and advancing the science. These disciplines include polymer science, catalysis, biomedicine, nanomaterials, and others. - Winner of a 2017 Textbook Excellence Award (Texty) from the Textbook and Academic Authors Association - Includes over 2,000 molecular structure drawings throughout the text - Features expanded coverage on applications of carboranes, particularly in biomedicine and nanomaterials, given the growth of research in these areas - Presents extended and updated tables, listing thousands of compounds with key literature references, provided online via the book's website - Explores the advances in practical applications for the many areas in which experts have discovered that carboranes afford new possibilities for solving problems and advancing the science
