Natural Products as Medicinally Useful Agents
1. Introduction
The use of natural products as medicinal agents presumably
predates the earliest recorded history as the earliest humans used various, but
specific plants to treat illness. Records from as early as 2700 B.C. from China,
traced to the Emperor Shennung, indicate the usefulness of plants for treating
disease, and the Ebers papyrus, written in about 1550 B.C., includes many of the
plants used in Egyptian medicine. Theophrastus (370-285 BC) began the scientific
classification of plants, and Dioscorides De Materia Medica (77 AD)
reported the uses, medicinal and otherwise, of over 600 plants. Ibn al-Baitar
(1197-1248) listed over 1400 drugs and medicinal plants in his Corpus of
Simples. In Europe, after the tenth century, much of the medicinal lore was
based in the church, particularly the monastic orders, but by the 1500’s,
after the invention of the printing press, herbals available to the general
public were popular, particularly in England. By the late 1700’s, studies like
William Withering’s An Account of the Foxglove and its Medicinal Uses
(1785) began to appear. These were based on case histories and described
specific doses and gave administration instructions for herbal remedies. In the
United States, before the advent of specific pharmaceuticals, herbal medicine
was relied upon to treat many illnesses. Development of drugs based on natural products has had a long history in the
United States, and in 1991, almost half of the best selling drugs were natural
products or derivatives of natural products. There has recently been a
resurgence of interest in herbal remedies, and a Reuters/Zogby poll in 2000
showed that 40% of people in the U.S. had tried herbal remedies. In 1998, the
U.S. market for natural supplements was over $12 billion in sales and increasing
by as much as 10% per year. Herbs such as St. John’s Wort, ginkgo, echinacea, and
ginseng are among the most popular herbs. In 1999, echinacea was reported to
make up 38% of the U.S. market, with ginkgo a close second at 34%. The efficacy
of these herbs is being investigated in many laboratories, and efforts are also
being made to isolate and identify any active constituents.
Natural products, as the term implies, are those chemical
compounds derived from living organisms, plants, animals, insects, and the study
of natural products is the investigation of their structure, formation, use, and
purpose in the organism. Drugs derived from natural products are usually
secondary metabolites and their derivatives, and today those must be pure and
highly characterized compounds. Until the late 1800's, organic chemistry was
almost exclusively the study and use of natural products.
The
purpose of these compounds in the organisms and their formation was little
understood or investigated, primarily due to the lack of appropriate techniques
and structural theory. The natural products that were studied and used tended to
be the compounds that occurred in the largest amounts, mostly in plants, and
were most easily isolated in a pure, or sometimes not very pure, form by
techniques such as simple distillation, steam distillation, or extraction with
acid or base. Originally teas or decoctions (aqueous extracts) or tinctures or
elixirs (alcoholic extracts) were used to prepare and administer herbal remedies
- these were usually the starting points for isolation work. We now employ
different solvents, e.g., ethanol to extract, hexane to concentrate
non-polar constituents, methanol to concentrate polar constituents, and modern
isolation techniques include all types of chromatography, often guided by
bioassays, to isolate the active compounds. Up until the 1950’s, the
structures of natural products, when determined, were determined by degradative
techniques, and a structure was not proven until the compound had been
synthesized in an unambiguous manner. Stereochemistry was not often determined.
Now, structures are elucidated primarily by spectroscopic techniques, and the
stereochemistry is an important feature of the structure.
The treatment of diseases with pure pharmaceutical agents is
a relatively modern phenomenon. However, as European explorers and merchants
spread out to the Western and Eastern parts of the world, some of the benefits
they would bring back were newly discovered pharmaceutical preparations of
natural origin. One of the earliest success stories in developing a drug from a
natural product was aspirin. The Ebers papyrus indicates the use of willow
leaves as an anitpyretic treatment, and early English herbals also recommend the
use of teas made from willow bark for this use. Following on these folk
treatments, chemists and pharmacists began to isolate the compounds responsible
for the remedy. Among the earliest pure compounds discovered was salicin,
isolated from the bark of the white willow, Salix alba, in 1825-26. It
was subsequently converted to salicylic acid
via hydrolysis and oxidation, and proved so successful as an antipyretic (fever
reducing) that it was actively manufactured and used worldwide. The use of
salicylic acid, however, often led to severe gastrointestinal toxicity. This was
overcome when Felix Hoffmann of Bayer Company converted salicylic acid into
acetylsalicylic acid (ASA) via acetylation. Bayer then began marketing ASA under
the trade name aspirin in 1899. Today, aspirin is still the most widely used
analgesic and antipyretic drug in the world.
- Alkaloids
- Terpenes
- Shikimic Acid and Polyketide Derived Natural Products
SUGGESTED READING/Web Sites
John Mann, Murder, Magic and Medicine, Oxford University Press, 1994.
Varro E. Tyler, Lynn R. Brady, and James E. Robbers, Pharmacognosy,
8th edition, Lea & Febiger, 1981.
Murray Goodman and Frank Morehouse, Organic Molecules in Action,
Gordon and Breach, 1973.
Lonnelle Aikman, Nature's Healing Arts - From Folk Medicine to Modern
Drugs, National Geographic Society, 1977.
Iwao Ojima, Pierre-Yves Bounaud, and Ralph J. Bernacki,
"Designing taxanes to treat multidrug-resistant tumors," Modern
Drug Discovery, May/June, 1999, pp. 45-52.
www.rain-tree.com
www.mobot.org/MOBOT/research/library
www.rph.wa.gov.au/labs/haem/malaria/history.html
www.globec.com.au/~mtbilbro/frcane.html
www.ibiblio.org/herbmed/eclectic/kings/main.html
www.who.int/health_topics/traditional_medicine/en/
(World Health Organization information on traditional medicines)
www.ncahf.org/pp/herbal.html
(National Council Against Health Fraud position paper on herbal remedies)
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