Anticancer Agents from Natural Products

"The search for new lead compounds is a crucial element of modern pharmaceutical research. Natural products provided the only source of pharmaceuticals for thousands of years, and natural products have made enormous contributions to human health through compounds such as quinine, morphine, aspirin (a natural product analog), digitoxin, and many others. The potential of natural products as anticancer agents was recognized in the 1950's by the U. S. National Cancer Institute (NCI) under the leadership of the late Dr. Jonathan Hartwell, and the NCI has since made major contributions to the discovery of new naturally occurring anticancer agents through its contract and grant support, including an important program of plant and marine collections. Many, although not all, of the compound classes described in the following pages owe their origin in whole or in part to NCI support. In spite of the success of the natural products approach to anticancer drug discovery, as exemplified by the following chapters, in recent years their importance as a source of molecular diversity for drug discovery research and development has been overshadowed by newer chemical approaches currently in favor. These approaches include chemical ones which make heavy use of combinatorial chemistry, and biological ones such as manipulation of biosynthetic pathways of microbial metabolites through combinatorial biosynthetic techniques. It is thus worthwhile to review briefly the major reasons why natural products are so important. First, there is a strong biological and ecological rationale for plants and marine invertebrates to produce novel bioactive secondary metabolites"--

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, TaxolR (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. He has established collaborations between the NCI and organizations in many countries promoting drug discovery from their natural resources. He has published over 150 chapters and 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 three 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 Sondheimer, and Dudley Williams. He moved to the State University of New York at Albany in 1966, and then to Virginia Tech 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 drug delivery of paclitaxel (Taxol^TM) using gold nanoparticles. He is the Principal Investigator of the Madagascar International Cooperative Biodiversity Group, which is working to achieve drug discovery, biodiversity conservation, and economic development in Madagascar. He received the Research Achievement Award of the American Society of Pharmacognosy in 1999, was named Virginia Scientist of the Year in 2002, and was the recipient of the American Chemical Society’s Ernest Guenther Award in the Chemistry of Natural Products in 2008. He has published over 350 papers and holds 15 patents. He is also an Elder in his church, the Blacksburg Christian Fellowship.


David J. Newman was born in Grays, Essex, England. First trained as an analytical chemis