Chemistry and Pharmacology of Anticancer Drugs

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Chemistry and Pharmacology of Anticancer Drugs

by David E. Thurston


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Publisher: CRC
Number Of Pages: 312
Publication Date: 2006-11-22

Book Description:

While drug therapies developed in the last 50 years have markedly improved the management of some types of cancers, treatment outcomes, and drug side-effects for the most common types remain unacceptable. However, recent technological advances are leading to improved therapies based on targeting distinct biological pathways in cancer cells. Chemistry and Pharmacology of Anticancer Drugs is a comprehensive survey of all families of anticancer agents currently in use or in advanced stages of clinical trials, including biologicals. The book is unique in providing molecular structures for all anticancer drugs, discussing them in terms of history, chemistry, mechanism of action, structure-function relationships, and pharmacology. It also provides some relevant information on side effects, dosing, and formulation. The author, a renowned scientist in cancer research and drug development, also provides up-to-date information on the drug discovery process, including new research tools, tumor-targeting strategies, and fundamental concepts in the emerging areas of personalized medicine (e.g., oncogenomics) and chemoprevention. Chemistry and Pharmacology of Anticancer Drugs is an indispensable resource for cancer researchers, medicinal chemists, and other biomedical scientists involved in the development of new anticancer treatments. Its breadth of coverage also makes it suitable for undergraduate and postgraduate courses in medicine, pharmacy, nursing, and related disciplines.


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Cisplatin: Chemistry and Biochemistry of a Leading Anticancer Drug

Cisplatin: Chemistry and Biochemistry of a Leading Anticancer Drug
by Bernhard Lippert


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Publisher: Wiley-VCH
Number Of Pages: 576
Publication Date: 1999-06-10
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

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