Anticancer Agents From Natural Products - G. Cragg, et al., (Taylor and Francis, 2005) WW

569 Pages·2005·40.29 MB·English

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ANTICANCER
AGENTS from
NATURAL
PRODUCTS

Edited by
Gordon M. Cragg
David G.I. Kingston
David J. Newman

Copyright © 2005 CRC Press, LLC

Published in 2005 by
CRC Press
Taylor & Francis Group
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© 2005 by Taylor & Francis Group, LLC
CRC Press is an imprint of Taylor & Francis Group

No claim to original U.S. Government works
Printed in the United States of America on acid-free paper
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International Standard Book Number-10: 0-8493-1863-7 (Hardcover)
International Standard Book Number-13: 978-0-8493-1863-4 (Hardcover)
Library of Congress Card Number 2004065568

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Library of Congress Cataloging-in-Publication Data

Kingston, David.
Anticancer agents from natural products / David Kingston, Gordon Cragg, David Newman.
p. cm.
ISBN 0-8493-1863-7
1. Antineoplastic agents. 2. Pharmacognosy. 3. Natural products. I. Cragg, Gordon M. L. II. Newman,
David J. III. Title.

RS431.A64K545 2005
616.99'4061--dc22
2004065568

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1863_Discl.fm Page 1 Thursday, May 12, 2005 10:43 AM

Copyright © 2005 CRC Press, LLC

Preface

Natural products have made an enormous contribution to cancer chemotherapy, and over half of
the current anticancer agents in clinical use are natural products or are derived from natural products.
In spite of this fact, no book published in recent years has brought together the disparate information
on anticancer natural products that is currently scattered throughout the chemical, biological, and
medical literature. The most recent book to do this was

Anticancer Agents Based on Natural Product
Models

, edited by John Cassady and John Douros, but this text was published in 1980 and is now
sadly out of date. The present book covers the current clinically used anticancer agents that are
either natural products or are clearly derived from natural product leads. In addition, a number of
drug candidates that are in clinical development are also covered, albeit more briefly, as many of
these will be clinically used drugs in the future.
It is expected that this volume will appeal to several classes of reader. It will be of interest to
natural products chemists, medicinal chemists, and pharmacognosists as an important reference
work in their area of interest. It will appeal to synthetic organic chemists as a source of information
on challenging synthetic targets. It will also appeal to oncologists as a source of background
information on the drugs they use, although it is not intended as a primary clinical text.
Some of the key features of the book include up-to-date coverage of a field that is scattered
among many different journals and review articles, inclusion of information on drugs in clinical
development, and authorship by leading scientists on each drug; in some cases the drug developer
or a close associate is the chapter author. These features should give the book real value for scientists
looking for information on the next generation of anticancer drugs.
The editors express their appreciation to the staff of Taylor & Francis for their excellent help,
especially Randi Cohen, Erika Dery, Lindsey Hofmeister, and Jay Margolis. The volume is dedicated
to the memory of those scientists who have blazed the trail to successful natural products-based
anticancer drug development, including Drs. John Douros, John Faulkner, Jonathan Hartwell, Morris
Kupchan, Paul Scheuer, Matthew Suffness, and Monroe Wall. May their tribe increase!

Gordon M. Cragg, David G. I. Kingston, and David J. Newman

Frederick, MD, and Blacksburg, VA

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Copyright © 2005 CRC Press, LLC

Editors

Gordon M. Cragg

was born in Cape Town, South Africa, and obtained his undergraduate training
in chemistry at Rhodes University before proceeding to Oxford University, where he obtained his
D. Phil. in organic chemistry in 1963. After 2 years of postdoctoral research in natural products
chemistry at the University of California, Los Angeles, he returned to South Africa to join the
Council for Scientific and Industrial Research. In 1966, he was appointed to the staff of the
Department of Chemistry at the University of South Africa and transferred to the University of
Cape Town in 1972. In 1979, he returned to the United States to join the Cancer Research Institute
at Arizona State University, working with Professor G. Robert Pettit on the isolation of potential
anticancer agents from plant and marine invertebrate sources. In 1985, he moved to the National
Cancer Institute in Bethesda, Maryland, and was appointed Chief of the Natural Products Branch
in 1989. His major interests lie in the discovery of novel natural product agents for the treatment
of cancer and AIDS. He has been awarded National Institutes of Health Merit Awards for his
contributions to the development of the 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). In 1998–1999 he served as
President of the American Society of Pharmacognosy, and was elected to honorary membership of
the society in 2003. He has established collaborations between the National Cancer Institute and
organizations in many countries promoting drug discovery from their natural resources. He has
given over 100 invited talks at conferences in many countries and has published more than 140
papers related to these interests.

David G. I. Kingston

was born in London, England, and obtained both his undergraduate and
graduate training in chemistry at Cambridge University. His graduate supervisors were Lord Todd
and Dr. D. W. Cameron, and his Ph.D. research was on the chemistry of the aphid pigments; he
completed his Ph.D. degree in 1963. He then did 3 years of postdoctoral research; one in the
Division of Biochemistry at MIT under Professor J. M. Buchanan and two back at Cambridge,
where he was a Research Fellow of Queens College and worked with Lord Todd, Franz Sondhe-
imer, and Dudley Williams. He moved to the State University of New York at Albany in 1966 and
then to Virginia Polytechnic Institute and State University in 1971, where he currently holds the
rank of University Distinguished Professor. He served as President of the American Society of
Pharmacognosy in 1988–1989. His research interests are on the isolation and structure elucidation
of novel natural products, especially those with anticancer activity, and on the chemistry and
mechanism of action of tubulin-binding natural anticancer agents such as taxol, epothilone, and
discodermolide, and he currently serves as the principal investigator of the Madagascar Interna-
tional Cooperative Biodiversity Group. He received the Research Achievement Award of the
American Society of Pharmacognosy in 1999 and was named Virginia Scientist of the Year in
2002. He has published over 280 papers and holds 14 patents. He is also an Elder in his church,
the Blacksburg Christian Fellowship.

David J. Newman

was born in Grays, Essex. Initially he trained as a chemical analyst (Grad. RIC),
followed by his being awarded an M.Sc. in organic chemistry (University of Liverpool), and then
after time in the U.K. chemical industry, he obtained a D. Phil. in microbial chemistry from the
University of Sussex in 1968. Following two years of postdoctoral studies on the structure of
electron transport proteins at the University of Georgia, he worked for Smith Kline and French in

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Copyright © 2005 CRC Press, LLC

Philadelphia, Pennsylvania, as a biological chemist predominantly in the area of antibiotic discovery.
During this time, he obtained an M.S. in information sciences in 1977 from Drexel University,
Philadelphia. He has worked for a number of United States-based pharmaceutical companies in
natural products-based discovery programs in antiinfective and cancer treatments and joined the
Natural Products Branch of the National Cancer Institute in 1991. He is responsible for the marine
and microbial collection programs of the National Cancer Institute and, in concert with Gordon
Cragg, for the National Cancer Institute’s Open and Active Repository programs. In 2003 he was
awarded the National Institutes of Health Merit Award for his contributions to the development of
potential anticancer agents from marine and microbial sources. His scientific interests are in the
discovery and history of novel natural products as drug leads in the antiinfective and cancer areas
and in the application of information technologies to drug discovery. In conjunction with Gordon
Cragg, he has established collaborations between the National Cancer Institute and organizations
in many countries promoting drug discovery from their natural resources. He has published over
60 papers, presented over 60 abstracts, holds 17 patents that are related to these interests, is both
a UK Chartered Chemist and a UK Chartered Biologist, and is also an adjunct full professor at the
Center of Marine Biotechnology, University of Maryland.

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Copyright © 2005 CRC Press, LLC

Contributors

Dr. Rima Al-awar

Eli Lilly and Company
Lilly Corporate Center
Discovery Chemistry Research
and Technology
Drop Code 2810
Indianapolis, IN 46285