Medicinal Chemistry

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Medicinal Chemistry
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But First Some Flowers
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15th Century Turkish Tulip
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Semper Augustus Tulip
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Triumph Tulips
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Queen of the Night Tulip
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Rosa alba White Rose of York England pre-16th
Century
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Madame Hardy Rose bred 1832
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Modern Hybrid Tea Rose
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Medicinal Chemistry

• Medicinal chemistry is the chemical study of
  chemical substances useful in medical treatments

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Diospyros lycioides source of chewing sticks in
Namibia
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Ceanothus americanus Native American chewing
stick
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Modern Chewing Sticks

• Most chewing stick plants have a wide range of
  antibacterial activity against a number of
  odontopathic bacterial species, and many also
  contained healing and/or analgesic compounds

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Bloodroot Sanguinaria canadensis
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Rhizome of Bloodroot
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Bloodroot extracts to treat dental plaque

• Bloodroot extracts have been identified as
  potentially valuable in controlling plaque
• Blood root has many alkaloids, known as
  sanguinaria alkaloids, and sanguinarine in
  particular, is thought to be a potential problem
  limiting the usefulness of blood root as a dental
  medicine
• There is an indication that sanguinarine may
  provoke glaucoma in predisposed humans and cats.

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Double Blind Testing

• A key component of western testing is to do
  double-blind testing, so neither healer nor
  patient knows what the patient is receiving.
• Such tests often involve the use of a real
  substance and a placebo.
• The test for the placebo effect assumes that
  patients are not expecting the substance to have
  certain effects.
• If patients do expect certain effects, it renders
  placebo testing difficult or impossible.

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Dwarf ginseng Panax trifolium
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Medicinal properties of Ginseng

• There are many claims that ginseng (Panax sp.
  F. Araliaceae the arums) increases sexual
  functioning, has anti-cancer properties, boosts
  the immune system, and even increases ability to
  perform in stressful situations.
• Difficult to test because ginseng preparations
  differ in their composition.
• Many of the chemicals produced by ginseng have
  counteractive effects. Isolated compounds work
  well in vitro, but simple ginseng preparations in
  vivo do not seem to have the benefits originally
  claimed. How ginsenosides are absorped,
  transported, degraded, and excreted is poorly
  known in humans.

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Opium poppy Papaver somniferum
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Plant chemical composition changes with
development

• The opium poppy Papaver somniferum is a good
  example of changes in metabolites during
  development. The seeds are free of alkaloids.
  After germination, the plant produces narcotine
  within 3 days. When the seedling is about 7 cm
  tall, the plant begins to produce codeine,
  morphine, and papaverine. Total alkaloid content
  slowly increases until flowering and then there
  is a sharp increase in alkaloids until the floral
  leaves fall off the plant.

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Poison hemlock Conium maculatum
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Poison hemlock in the wild
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Water hemlock Cicuta virosa
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Poison Hemlocks

• Poison hemlock and the water hemlocks are the
  most poisonous plants in North America. The
  active ingredient in poison hemlock is the
  alkaloid coniine. It is a central nervous system
  stimulant that affects the body like a nicotine
  overdose paralysis creeps from the lower limbs
  upward. Death is due to the paralysis of the
  diaphragm and subsequent respiratory failure.
  Water hemlocks are toxic due to an alcohol,
  cicutoxin. It produces violent convulsions and
  death.

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Alkaloid content varies during the day

• In poison hemlock, the amount of coniine varies
  during the day. The fruits are very high in
  coniine at 4 a.m. (226 micrograms) and low in
  coniine by 4 p.m. (8 micrograms). The amount of
  coniine varies with amount of sun as well.
  Another relative, wild parsnip (Pastinaca sativa)
  is toxic to the skin and is more toxic during
  bright sun than in cloudy weather or at night.

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Wild parsnip Pastinaca sativa
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Wild parsnip in the field
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Teonanacatl The Flesh of the Gods
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Psilocybe mushrooms
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Dr. Albert Hoffman Swiss Chemist
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Conocybe also produces psilocin
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Panaeolus also produces psilocin, may be toxic
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Stropharia also produces psilocin, may be toxic
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Chemical structures of several hallucinogenic
substances
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Drug Similarities

• Interestingly, the drug Visken, used to treat
  hypertension was developed as an analog to
  4-hydroxyindole, the phenolic nucleus of
  psilocybin and psilocin, from chemicals in Albert
  Hoffmans lab.