2nd Edition

Anticancer Agents from Natural Products

    784 Pages 450 B/W Illustrations
    by CRC Press

    The approach to drug discovery from natural sources has yielded many important new pharmaceuticals inaccessible by other routes. In many cases the isolated natural product may not be an effective drug for any of several reasons, but it nevertheless may become a drug through chemical modification or have a novel pharmacophore for future drug design. In summarizing the status of natural products as cancer chemotherapeutics, Anticancer Agents from Natural Products, Second Edition covers the:

    • History of each covered drug—a discussion of its mechanism on action, medicinal chemistry, synthesis, and clinical applications
    • Potential for novel drug discovery through the use of genome mining as well as future developments in anticancer drug discovery
    • Important biosynthetic approaches to "unnatural" natural products

    Anticancer Agents from Natural Products, Second Edition discusses how complex target-oriented synthesis—enabled by historic advances in methodology—has enormously expanded the scope of the possible. This book covers the current clinically used anticancer agents that are either natural products or are clearly derived from natural product leads. It also reviews drug candidates currently in clinical development since many of these will be clinically used drugs in the future.

    Examples include the drugs etoposide and teniposide derived from the lead compound podophyllotoxin; numerous analogs derived from taxol; topotecan, derived from camptothecin; and the synthetic clinical candidates, E7389 and HTI-286, developed from the marine leads, halichondrin B and hemiasterlin.

    Introduction
    Gordon M. Cragg, David G. I. Kingston, and David J. Newman
    Camptothecin and Its Analogs
    Nicolas J. Rahier, Craig J. Thomas, and Sidney M. Hecht
    The Discovery and Development of the Combretastatins
    Kevin G. Pinney, George R. Pettit, Mary Lynn Trawick, Christopher Jelinek, and David J. Chaplin
    Homoharringtonine and Related Compounds
    Hideji Itokawa, Yukio Hitotsuyanagi, and Kuo-Hsiung Lee
    Podophyllotoxins and Analogs
    Kuo-Hsiung Lee and Zhiyan Xiao
    Taxol and its Analogs
    David G. I. Kingston
    The Vinca Alkaloids
    Fanny Roussi, Françoise Guéritte, and Jacques Fahy
    The Bryostatins
    David J. Newman
    The Isolation, Characterization, and Development of a Novel Class of Potent Antimitotic Macrocyclic Depsipeptides: The Cryptophycins
    Rima S. Al-awar and Chuan Shih
    Chemistry and Biology of the Discodermolides, Potent Mitotic Spindle Poisons
    Sarath P. Gunasekera and Amy E. Wright
    The Dolastatins: Novel Antitumor Agents from Dolabella auricularia
    Erik Flahive and Jayaram Srirangam
    Ecteinascidin-743 (Yondelis®), Aplidin®, and Irvalec®
    Carmen Cuevas, Andrés Francesch, Carlos M. Galmarini, Pablo Avilés, and Simon Munt
    Discovery of E7389, a Fully Synthetic Macrocyclic Ketone Analog of Halichondrin B
    Melvin J. Yu, Yoshito Kishi, and Bruce A. Littlefield
    HTI-286 (Taltobulin), A Synthetic Analog of the Antimitotic Natural Product Hemiasterlin
    Raymond J. Andersen, David E. Williams, Wendy K. Strangman, and Michel Roberge
    The Actinomycins
    Anthony B. Maugera and Helmut Lackner
    Anthracyclines
    Federico-Maria Arcamone
    Ansamitocins (Maytansinoids)
    Tin-Wein Yu, Heinz G. Floss, Gordon M. Cragg, and David J. Newman
    Benzoquinone Ansamycins
    Kenneth M. Snader
    Bleomycin Group Antitumor Agents
    Sidney M. Hecht
    Biochemical and Biological Evaluation of (+)-CC-1065 Analogs and Conjugates with Polyamides
    Rohtash Kumar and J. William Lown
    Epothilone, a Myxobacterial Metabolite With Promising Antitumor Activity
    Gerhard Höfle and Hans Reichenbach
    Enediynes
    Philip R. Hamann, Janis Upeslacis, and Donald B. Borders
    The Mitomycins
    William A. Remers
    Staurosporines and Structurally Related Indolocarbazoles as Antitumor Agents
    Michelle Prudhomme
    Combinatorial Biosynthesis of Anticancer Natural Products
    Steven G. Van Lanen and Ben Shen
    Developments and Future Trends in Anticancer Natural Products Drug Discovery
    Gordon M. Cragg and David J. Newman
    Index

    Biography

    Gordon M. Cragg obtained his undergraduate training in chemistry at Rhodes University, South Africa, and his D. Phil. (organic chemistry) from Oxford University. After two years of postdoctoral research at the University of California, Los Angeles, he returned to South Africa to join the Council for Scientific and Industrial Research. In 1966, he joined the Chemistry Department at the University of South Africa, and transferred to the University of Cape Town in 1972. In 1979, he returned to the US to join the Cancer Research Institute at Arizona State University working with Professor G. R. Pettit. In 1985, he moved to the National Cancer Institute (NCI), National Institutes of Health (NIH) in Bethesda, Maryland, and was appointed Chief of the NCI Natural Products Branch in 1989. He retired in December, 2004, and is currently serving as an NIH Special Volunteer. His major interests lie in the discovery of novel natural product agents for the treatment of cancer and AIDS, with an emphasis on multidisciplinary and international collaboration. He has given over 100 invited talks at conferences in many countries worldwide, and has been awarded NIH Merit Awards for his contributions to the development of the anticancer drug, Taxol (1991), leadership in establishing international collaborative research in biodiversity and natural products drug discovery (2004), and contributions to developing and teaching NIH technology transfer courses (2004). He was President of the American Society of Pharmacognosy in 1998-1999, was elected to Honorary Membership of the Society in 2003, and was named a Fellow of the Society in 2008. In November 2006 he was awarded the William L. Brown Award for Plant Genetic Resources by Missouri Botanical Garden which also named a recently discovered Madagascar plant in his honor, Ludia craggiana, and in April 2010 he was awarded an Honorary Doctorate of Science by his South African alma mater, Rhodes University.

    "…maintains the extremely high standards of the first edition…. Over the past few years, a comparatively large number of anticancer agents of natural product origin have been brought to the market, so this expanded and updated volume is of very high relevance to members of the biomedical research community. The authors and editors of this second edition deserve heartfelt congratulations for compiling such an informative and inspiring volume, which serves as a major addition to the natural products literature."
    —A. Douglas Kinghorn, The Ohio State University, Columbus, in Journal of Natural Products

    Praise for the Previous Edition

    "The book brings home to us not only the amazing chemical complexity of the natural world but also the vast reservoir of potential new healing agents that yet remain to be tapped. This impressive work, which maintains a uniformly high standard throughout, will be of major benefit to a wide readership… .It seems likely that it will remain the definitive work in its genre for many years to come."
    Chemistry World

    "Edited by leading scientists who have contributed enormously to natural product development and potential anticancer natural products, Anticancer Agents from Natural Products is a convenient summary of the current status of research and development of some of the most effective anticancer agents available today. It is an ideal foundation for scientist engaged in developing new and improved drugs based on natural sources."
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