Skip to main content

Natural Product Drug Discovery and Development

The United States National Cancer Institute Role

  • Chapter
Phytochemicals in Human Health Protection, Nutrition, and Plant Defense

Part of the book series: Recent Advances in Phytochemistry ((RAPT,volume 33))

Abstract

Over the ages, humans have relied on nature for their basic needs for the production of foodstuffs, shelters, clothing, means of transportation, fertilizers, flavors and fragrances, and not least, medicines. Plants have formed the basis of sophisticated traditional medicine systems that have been in existence for thousands of years in countries such as China1 and India.2 These plant-basedsystems continue to play an essential role in health care, and it has been estimated by the World Health Organization that approximately 80% of the world’s inhabitants rely mainly on traditional medicines for their primary health care.3 Plant products also play an important role in the health care systems of the remaining 20% of the population mainly residing in developed countries. Analysis of data on prescriptions dispensed from community pharmacies in the United States from 1959 to 1980 indicates that about 25% contained plant extracts or active principles derived from higher plants, and at least 119 chemical substances, derived from 90 plant species, can be considered as important drugs currently in use in one or more countries.3 Of these 119 drugs, 74% were discovered as a result of chemical studies directed at the isolation of the active substances from plants used in traditional medicine. Well-known examples of plant-derived medicinal agents include: the antimalarial drug quinine, obtained from the bark of Cinchona officinalis; the analgesics, codeine and morphine from Papaver somniferum; the antihypertensive reserpine from Rauwolfia serpentina; and the cardiac glycoside, digoxin, from Digitalis purpurea.4

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Similar content being viewed by others

References

  1. CHANG, H-M, BUT, PP-H. 1986. Pharmacology and Applications of Chinese Materia Medica, Vols 1 and 2, Singapore, World Scientific Publishing.

    Google Scholar 

  2. KAPOOR, L.D. 1990. CRC Handbook of Ayurvedic Medicinal Plants. Boca Raton, Florida, CRC Press.

    Google Scholar 

  3. FARNSWORTH, N.R., AKERELE, O., BINGEL, A.S., SOEJARTO, D.D., GUO, Z. 1985. Medicinal plants in therapy. Bull. WHO. 63: 965–981.

    CAS  PubMed  Google Scholar 

  4. KINGHORN A.D. 1994. The discovery of drugs from higher plants. In: The Discovery of Natural Products with Therapeutic Potential (VP Gullo, ed.), Butterworth-Heinemann, Boston, pp. 81–108.

    Google Scholar 

  5. MCCONNEL, O., LONGLEY, R.E., KOEHN, F.E. 1994. The discovery of marine natural products with therapeutic potential. In: The Discovery of Natural Products with Therapeutic Potential (VP Gullo, ed.), Butterworth-Heinemann, Boston, pp. 109–174.

    Google Scholar 

  6. CRAGG, G.M., NEWMAN, D.J., SNADER, K.M. 1997. Natural products in drug discovery and development. J. Nat. Prod. 60: 52–60.

    Article  CAS  PubMed  Google Scholar 

  7. HARTWELL J.L. 1982. Plants Used Against Cancer. Quarterman, Lawrence, MA.

    Google Scholar 

  8. CRAGG, G.M., BOYD, M.R., CARDELLINA II, J.H., NEWMAN, D.J., SNADER, K.M., MCCLOUD, T.G. 1994. Ethnobotany and drug discovery: The experience of the US National Cancer Institute. In: Ethnobotany and the Search for New Drugs. Ciba Foundation Symposium 185, (DJ Chadwick, J Marsh, eds.), Wiley & Sons, Chichester, U.K., pp. 178–196.

    Google Scholar 

  9. DRISCOLL, J.S. 1984. The preclinical new drug research program of the National Cancer Institute. Cancer Treat. Rep. 68: 63–76.

    CAS  PubMed  Google Scholar 

  10. POTMEISEL, M., PINEDO, H. 1995. Camptothecins: New Anticancer Agents. Boca Raton, Florida, CRC Press.

    Google Scholar 

  11. CRAGG, G.M., BOYD, M.R., CARDELLINA II, J.H., GREVER, M.R., SCHEPARTZ, S.A., SNADER, K.M., SUFFNESS, M. 1993. Role of plants in the National Cancer Institute drug discovery and development program. In: Human Medicinal Agents from Plants. Am Chem Soc Symposium Series 534, (AD Kinghorn, MF Balandrin, eds.), Amer. Chem. Soc, Washington, DC, pp. 80–95.

    Chapter  Google Scholar 

  12. CHRISTIAN, M.C., PLUDA, J.M., HO, T.C., ARBUCK, S.G., MURGO, A.J., SAUSVILLE, E.A. 1997. Promising new agents under development by the Division of Cancer Treatment, Diagnosis, and Centers of the National Cancer Institute. Sem. Oncol. 24: 219–240.

    CAS  Google Scholar 

  13. PHILIP, P.A., REA, D., THAVASU, P., CARMICHEL, J., STUART, N.S.A., ROCKETT, H., TALBOT, D.C., GANESAN, T., PETTIT, G.R., BALKWILL, F., HARRIS, A.L. 1993. Phase I study of bryostatin 1: Assessment of interleukin 6 and tumor necrosis factor alpha induction in vivo. J. Natl. Cancer Inst. 85: 1812–1818.

    Article  CAS  PubMed  Google Scholar 

  14. BOYD, M.R., PAULL, K.D. 1995. Some practical considerations and applications of the National Cancer Institute in vitro anticancer drug discovery screen. Drug Dev. Res. 34: 91–109.

    Article  CAS  Google Scholar 

  15. MAYS, TD, MAZAN, K.D., CRAGG, G.M., BOYD, M.R. 1997. “Triangular privity”-a working paradigm for the equitable sharing of benefits from biodiversity research and development. In: Global Genetic Resources: Access, Ownership, and Intellectual Property Rights, (KE Hoagland and AY Rossman, eds.), Association of Systematics Collections, Washington DC, pp. 279–298.

    Google Scholar 

  16. BOYD, M.R. 1988. Strategies for the identification of new agents for the treatment of AIDS: A national program to facilitate the discovery and preclinical development of new candidates for clinical evaluation. In: “AIDS: Etiology, Diagnosis, Treatment and Prevention” (VT. De Vita, S. Hellman and S.A. Rosenberg, eds.), J.B. Lippincott, Philadelphia, pp. 305–319.

    Google Scholar 

  17. WEISLOW, O.S., KISER, R., FINE, D.L, BADER, J., SHOEMAKER, R.H., BOYD, M.R. 1989. New soluble-formazan assay for HIV-1 cytopathic effects: Application to high-flux screening of synthetic and natural products for AIDS-antiviral activity. J. Natl. Cancer Inst. 81: 577–586.

    Article  CAS  PubMed  Google Scholar 

  18. CRAGG, G.M., SCHEPARTZ, S.A., SUFFNESS, M., GREVER, M.R. 1993. The taxol supply crisis. New NCI policies for handling the large-scale production of novel natural product anticancer and anti-HIV agents. J. Nat. Prod. 56: 1657–1668.

    Article  CAS  PubMed  Google Scholar 

  19. HORWITZ, S.B. 1992. Mechanism of action of taxol. Trends Pharmacol. Sci. 13: 134–136.

    Article  CAS  PubMed  Google Scholar 

  20. MCQUIRE, W.P., ROWINSKY, E.K., ROSENSHEIM, N.B., GRUMBINO, EC, CETTINGER, D.S., ARMSTRONG, D.K., DONEHOWER, R.C. 1989. Taxol: A unique antineoplastic agent with significant activity in advanced ovarian epithelial neoplasms. Ann. Intern. Med. 111: 273–279.

    Google Scholar 

  21. DENIS, J.N., GREENE, A.E., GUENARD, D., GUERITTE-VOEGELEIN, F., MANGATAL, L., POTIER, P. 1988. Highly efficient, practical approach to natural taxol. J. Am. Chem. Soc. 110: 5917–5919.

    Article  CAS  Google Scholar 

  22. HOLTON, R.A., LIU, J.H., GENTILE, L.N., BEIDIGER, RJ. 1992. Semi-synthesis of taxol. Second NCI Workshop on Taxol and Taxus, Alexandria, VA, National Cancer Institute, September, 1992;

    Google Scholar 

  23. GEORG, G.I., CHERUVALLATH, Z.S., HIMES, R.H., MEJILLANO, M.R. 1992. Novel biologically active taxol analogues: Baccatin III 13-[N-p-chlorobenzoyl-(2′R,3′S)-3′-phenylisoserinate] and baccatin III 13[N-benzoyl-(2′,R,3′S)-3′,-(p-chlorophenyl)isoserinate]. Bioorg Med Chem Lett. 2: 295–298.

    Article  CAS  Google Scholar 

  24. CORTES, J.E., PAZDUR, R. 1995. Docetaxel. J. Clin. Oncol. 13: 2643–2655.

    CAS  Google Scholar 

  25. Paclitaxel production, marketing heats up. Chem. & Eng. News, 1998, June 15:11

    Google Scholar 

  26. STROBEL, G.A., HESS, W.M., FORD, E., SIDHU, R.S., YANG, X. 1996. Taxol from fungal endophytes and the issue of biodiversity. J. Industrial Microbiology 17: 417–423.

    Article  CAS  Google Scholar 

  27. BOYD, M.R., HALLOCK, Y.F., CARDELLINA, J.H., II, MANFREDI, K.P., BLUNT, J.W., MCMAHON, J.B., BUCKHEIT, R.W., JR., BRINGMANN, G., SCHAFFER, M., CRAGG, G.M., THOMAS, D.W, JATO, J.G. 1994. Anti-HIV michellamines from Ancistrocaldus korupensis. J. Med. Chem. 37: 1740–1745.

    Article  CAS  PubMed  Google Scholar 

  28. THOMAS, D.W., GEREAU, R.E. 1993. Ancistrocladus korupensis (Ancistroclada ceae): A New Species of Liana from Cameroon. Novon. 3: 494–498.

    Article  Google Scholar 

  29. BRINGMANN, G., HARMSEN, S., HOLENZ, J., GEUDER, J., GOTZ, R., KELLER, P.A., WALTER, R., HALLOCK, Y.F., CARDELLINA, J.H., II, BOYD, M.R. 1994. “Biomimetic” oxidative dimerization of korupensamine A: Completion of the first total synthesis of michellamines A, B, and C. Tetrahedron. 50: 9643–9648.

    Article  CAS  Google Scholar 

  30. HALLOCK, Y.F., MANFREDI, K.P., BLUNT, J.W., CARDELLINA, J.H., II, SCHAFFER, M., GLUDEN, K-P., BRINGMANN, G, LEE, A.Y., CLARDY, J., FRANCOIS, G., BOYD, M.R. 1994. Korupensamines A—D, novel antimalarial alkaloids from Ancistrocladus korupensis. J. Org. Chem. 59: 6349–6355.

    Article  CAS  Google Scholar 

  31. SUFFINESS, M, CRAGG, G.M., GREVER, M.R., GRIFO, F.J., JOHNSON, G., MEAD, J.A.R., SCHEPARTZ, S.A., VENDITTI, J.M., WOLPERT, M. 1995. The National Cooperative Natural Products Drug Discovery Group (NCNPDDG) and International Cooperative Biodiversity Group (ICBG) Programs. Internat. J. Pharmacognosy. 33 Supplement: 5–16.

    Google Scholar 

  32. BAKER, J.T., BORRIS, R.P., CARTE, B, CRAGG. G.M., GUPTA, M.P., IWU, M.M., MADULID, D.R., TYLER, V.E. 1995. Natural product drug discovery and development: New perspectives on international collaboration. J. Nat. Prod. 58: 1325–1357.

    Article  CAS  PubMed  Google Scholar 

  33. KASHMAN, Y., GUSTAFSON, K.R., FULLER, R.W., CARDELLINA, J.H., II, MCMAHON, J.B., CURRENS, M.J., BUCKHEIT, R.W, HUGHES, S.H., CRAGG, G.M., BOYD, M.R. 1992. The Calanolides, a novel HIV-inhibitory class of coumarin derivatives from the tropical rainforest tree, Calophyllum langerum. J. Med. Chem. 35: 2735–2743.

    Article  CAS  PubMed  Google Scholar 

  34. FLAVIN, M.T., RIZZO, J.D., KHILEVICH, A., KUCHERENKO, A., SHEINKMAN, A.K., VILAYCHACK, V, LIN, L., CHEN, W., GREENWOOD, E.M., PENGSUPARP, T., PEZZUTO, J, HUGHES, S.H., FLAVIN, T.M., CIBULSKI, M., BOULANGER, W.A., SHONE, R.L., XU, Z.-Q. 1996. Synthesis, chromatographic resolution, and anti-human immunodeficiency virus activity of (±)-calanolide A and its enantiomers. J. Med. Chem. 39: 1303–1313.

    Article  CAS  PubMed  Google Scholar 

  35. TENKATE, K, WELLS, A. 1998. Benefit-Sharing Case Study. The access and benefit-sharing policies of the United States National Cancer Institute: a comparative account of the discovery and development of the drugs Calanolide andTopotecan. Submission to the Executive Secretary of the Convention on Biological Diversity by the Royal Botanic Gardens, Kew.

    Google Scholar 

  36. ROSENTHAL, J. 1997. OECD Proceedings: Investing in Biological Diversity. The Cairns Conference, Australia, 25–28 March, 1996. OECD Publications, Paris, pp. 253–273.

    Google Scholar 

  37. BALANDRIN, M.F., KINGHORN, A.D., FARNSWORTH, N.R. 1993. Plant-derived natural products in drug discovery and development. An overview. In: Human Medicinal Agents from Plants (AD Kinghorn and MF Balandrin, eds.) Am. Chem. Soc. Symposium Series 534, Amer. Chem. Soc, Washington, DC, pp. 2–12.

    Chapter  Google Scholar 

  38. YOUNG, P. 1997. Major microbial diversity initiative recommended. ASM News. 63: 417–421.

    Google Scholar 

  39. SAUSVILLE, E.A. 1997. Targeted toxins. In: Encyclopedia of Cancer, Vol. III. Academic Press, Inc., pp. 1703–1714.

    Google Scholar 

  40. MELTON, R.G., SHERWOOD, R.F. 1996. Antibody-enzyme conjugates for cancer therapy. J. Natl. Cancer Inst. 88: 153–165.

    Article  CAS  PubMed  Google Scholar 

  41. MCDANIEL, R., EBERT-KHOSLA, S., HOPWOOD, D.A., KHOSLA, C. 1995. Rational design of aromatic polyketide natural products by recombinant assembly of enzymatic units. Nature. 375: 549–554.

    Article  CAS  PubMed  Google Scholar 

  42. HORAN, A.C. 1994. Actinomycetes: A continuos source of novel natural products. In: The Discovery of Natural Products with Therapeutic Potential (VP Gullo, ed.), Butterworth-Heinemann, Boston, pp. 3–30.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1999 Springer Science+Business Media New York

About this chapter

Cite this chapter

Cragg, G.M., Boyd, M.R., Khanna, R., Newman, D.J., Sausville, E.A. (1999). Natural Product Drug Discovery and Development. In: Romeo, J.T. (eds) Phytochemicals in Human Health Protection, Nutrition, and Plant Defense. Recent Advances in Phytochemistry, vol 33. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4689-4_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-4689-4_1

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7123-6

  • Online ISBN: 978-1-4615-4689-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics