Med Chem 1 Flashcards
Pharmacognosy is…
…the study of the physical, chemical, biochemical, and
biological properties of drugs, drug substances, or
potential drugs or drug substances of natural origin, as
well as the search for new drugs from natural sources
Natural Drugs…
Natural product screening
What pools can we take from?
• Plant kingdom (e.g. Morphine, cocaine, salicin, quinine, taxol)
• Microbial world (e.g. Penicillin and statins)
• Marine world (e.g. curacin A, obtained from a marine cyanobacterium)
• Animals (e.g. Epibatidine from the skin of the Ecuadorian poison frog)
• Toxins (venoms) (e.g. Teprotide, a peptide isolated from the venom of the Brazilian pit viper)
The plant kingdom
-is a plentiful, rich supply of complex &
varied chemical compounds
Plant species in Rainforest:
- untapped source
- still waiting to be discovered
Plant Extracts
Plants did not evolve for the purpose of producing medicines
~ 320,000 plant species on the planet
25,000 used in folk medicine
Only 120 active principles used around the world
UK has < 40 in regular use
• Chemicals in plants
- many have a role as irritants or toxic materials that provide
defense against predators (herbivores, omnivores)
Herbal Remedies
• Experimentation with berries, leaves & roots
• Local healer brews
• Often useless & dangerous
• Example of Placebo effect - state of mind, no real differences
• 80% of worlds population use herbal drugs as part of their normal health care routine
• In the USA it is the fastest growing segment of pharmacy trade
• They tend to be far less expensive than prescription drugs
• They are not pure substances (they contain many consitituents)
• They are not standardised or analysed for the
content of the active principle
• Definition of a herb:
- a crude material containing multiple
pharmacologically active compounds - Is a substance of plant origin
- May contain dozens of different compounds
- Can have its composition (and quality) verified using HPLC
- May contain some compounds that reinforce others
Herbal medicines may work through..
synergy
In other words, the mixture acts together (many complex
structures and interactions) to generate a beneficial effect
Example of interaction
A patient taking coumadin (warfarin) who also starts taking ginkgo (= gingko) biloba extracts (which affects platelet-activating factor, PAF) can effectively cause an overdose effect of
coumadin leading to bleeding as a result of
excessive blood thinning.
Ginkgo biloba extracts
Ginkgo biloba extracts include ginkgolide A and B
Ginkgo biloba extracts produce vasodilatory effects on both the arterial and venous circulation (increasing both peripheral &
cerebral blood flow)
Chinese herbal medicine
produced antimalarial agent (artemisinin)
A good illustration of how natural products tend to be:
- complex structures and therefore novel
- hard to synthesise in the lab
Natural Drugs…
Reserpine - From the Indian snakeroot plant
- Indole nucleus
- Light yellow crystalline alkaloid
- Breaks down in presence on light (especially in clear glass containers)
- Able to reduce blood pressure
Natural Drugs…
SALICIN
• A glycoside
• Isolated in 1829
• Synthesised in 1979
- 1870 Marcellus von Nencki showed salicin is converted in the body to salicylic acid (antipyretic)
Natural Drugs…
QUININE
The Quechua Indians of Peru used the bark of the Cinchona tree as a muscle relaxant, thus stopping the shivering brought on by cold weather.
The active ingredient in this remedy is quinine which is now used to treat malaria.
• Arrests patient fevers
• Variable responses of patients to treatment with cinchona bark
• Led to isolation of active principle (1811, Bernardino Gomez,
Portuguese surgeon, isolated silvery crystals)
Natural Drugs… names
- Morphine from the opium poppy - Ancient Egypt
- Reserpine from the snake-root plant - India
- Salicin from the willow tree - Medieval England
- Quinine from cinchona bark - Aztecs (S. America)
More recent examples of natural drugs…
Combretastatin
• Isolated (in 1982) from the South African tree Combretum caffrum
• A potent cytotoxic against a wide variety of human cancer cells
• Poor water solubility is the main drawback
• Still in clinical trials but may be the next anticancer drug of choice
TAXOL® (Paclitaxel)
• Screening program in 1960 by US National cancer institute
• Used plants gathered by US Department of Agriculture (bark,
twigs, leaves & fruit of the Pacific Yew tree)
• in vitro studies showed Taxol® had cytotoxic activity
• Chemical structure reported in 1971
• Synthesised in 1994 by 2 groups
• R.A. Holton (Florida State University)
• K.C. Nicolaou (Scripps Research Institute)
Used in:
Ovarian cancer
Metastatic breast cancer
Lung cancer
Prostate cancer
