Intro of Cognosy

1. S1 L1 Introduction to
Pharmacognosy
Anna Drew
with slide contribution from Bob Hoffman
& grateful acknowledgement for inspirational teaching received at the
School of Pharmacy, University of London

2. • ‘Pharmacognosy’
– pharmakon ‘a drug’ (Greek)
– gignosco ‘ to acquire knowledge of’ (Greek)
– OR cognosco ‘to know about’ (Latin)
• Johann Adam Schmidt (1759-1809)
– Lehrbuch der Materia Medica
– Published Vienna 1811
– Beethoven’s physician

3. Naturally occurring substances having
a medicinal action:
• Surgical dressings prepared from natural fibres
• Flavourings and suspending agents
• Disintegrants
• Filtering and support media
• Other associated fields:
– Poisonous and hallucinogenic plants
– Raw materials for production of oral contraceptives
– Allergens
– Herbicides and insecticides

4. Pharmacognosy is related to:
– Botany
– Ethnobotany
– Marine biology
– Microbiology
– Herbal medicine
– Chemistry (phytochemistry)
– Pharmacology
– Pharmaceutics

5. Skills & techniques valuable elsewhere:
Analysis of other commodoties
• Foods, spices, gums, perfumes, fabrics, cosmetics
Used by
• Public analysts, forensic sciences, quality-control scientists
Role in pure sciences
• Botany, plant taxonomy, phytochemistry
Botanists and chemists looking at:
• Chemical plant taxonomy, genetic/enzymatic studies involving 2y
metabolites
• Artificial and tissue culture
• Effects of chemicals on plant metabolites
• Induction of abnormal syntheses
• Bioassay-guided isolation techniques

6. Vegetable drugs can be arranged for study:
– Alphabetical
– Taxonomic**
• botanical classification
– Morphological
• Organised drugs: leaves, flowers, fruit, seeds etc
• Unorganised drugs: extracts, gums, resins, oils etc
– Pharmacological/therapeutic*
• Increasingly used with screening
• Constituents of one drug may fall into several groups
– Chemical/biogenetic
• Constituents or biosynthetic pathways

7. CLASS Angiospermae (Angiosperms) Plants which produce flowers
Gymnospermae (Gymnosperms) Plants which don't produce flowers
SUBCLASS Dicotyledonae (Dicotyledons, Dicots) Plants with two seed leaves
Monocotyledonae (Monocotyledons, Monocots) Plants with one seed leaf
SUPERORDER A group of related Plant Families, classified in the order in which they are thought to have
developed their differences from a common ancestor.
There are six Superorders in the Dicotyledonae (Magnoliidae, Hamamelidae, Caryophyllidae,
Dilleniidae, Rosidae, Asteridae), and four Superorders in the Monocotyledonae
(Alismatidae, Commelinidae, Arecidae, Liliidae)
The names of the Superorders end in -idae
ORDER Each Superorder is further divided into several Orders.
The names of the Orders end in -ales
FAMILY
Each Order is divided into Families. These are plants with many botanical features in common,
and is the highest classification normally used. At this level, the similarity between plants
is often easily recognisable by the layman.
Modern botanical classification assigns a type plant to each Family, which has the particular
characteristics which separate this group of plants from others, and names the Family after
this plant.
The number of Plant Families varies according to the botanist whose classification you follow.
Some botanists recognise only 150 or so families, preferring to classify other similar plants
as sub-families, while others recognise nearly 500 plant families. A widely-accepted
system is that devised by Cronquist in 1968, which is only slightly revised today.
The names of the Families end in -aceae
SUBFAMILY The Family may be further divided into a number of sub-families, which group together plants
within the Family that have some significant botanical differences.
The names of the Subfamilies end in -oideae

8. TRIBE A further division of plants within a Family, based on smaller botanical differences, but still usually
comprising many different plants.
The names of the Tribes end in -eae
SUBTRIBE A further division, based on even smaller botanical differences, often only recognisable to botanists.
The names of the Subtribes end in -inae
GENUS This is the part of the plant name that is most familiar, the normal name that you give a plant - Papaver
(Poppy), Aquilegia (Columbine), and so on. The plants in a Genus are often easily recognisable as
belonging to the same group.
The name of the Genus should be written with a capital letter.
SPECIES This is the level that defines an individual plant. Often, the name will describe some aspect of the plant
- the colour of the flowers, size or shape of the leaves, or it may be named after the place where it
was found. Together, the Genus and species name refer to only one plant, and they are used to
identify that particular plant. Sometimes, the species is further divided into sub-species that
contain plants not quite so distinct that they are classified as Varieties.
The name of the species should be written after the Genus name, in small letters, with no capital letter.
VARIETY A Variety is a plant that is only slightly different from the species plant, but the differences are not so
insignificant as the differences in a form. The Latin is varietas, which is usually abbreviated to var.
The name follows the Genus and species name, with var. before the individual variety name.
FORM A form is a plant within a species that has minor botanical differences, such as the colour of flower or
shape of the leaves.
The name follows the Genus and species name, with form (or f.) before the individual variety name.
CULTIVAR A Cultivar is a cultivated variety, a particular plant that has arisen either naturally or through deliberate
hybridisation, and can be reproduced (vegetatively or by seed) to produce more of the same plant.
The name follows the Genus and species name. It is written in the language of the person who
described it, and should not be translated. It is either written in single quotation marks or has cv.
written in front of the name.

9. Example
• Linnaeus (1707-1778), Swedish biologist
• Division Angiospermae
• Class Dicotyledoneae
• Subclass Sympetalae
• Order Tubiflorae
• Suborder Verbenineae
• Family Labiatae (Lamiaceae)
• Subfamily Stachydoideae
• Tribe Satureieae
• Genus Mentha
• Species Mentha piperita Linnaeus (peppermint)
• Varieties Mentha piperita var. officinalis Sole
(White Peppermint); Mentha piperita var.
vulgaris Sole (Black Peppermint)

10. Contribution of plants to
medicine and pharmacy
• 18th
century drugs plant based
• 19th
century a range of drugs was isolated:
• 1805 morphine
• 1817 emetine
• 1819 strychnine
• 1820 quinine
• Famous plants/plant drugs?

11. Quinine
• Cinchona bark, South American tree
• Used by Incas; dried bark ground and mixed
with wine
• First used in Rome in 1631
• Extracted 1820
• Large scale use 1850
• Chemical synthesis 1944
• Actual tree remains the most economic source

12. Belladonna -> atropine
Anticholinergic
syndrome:
• Hot as hell
• Blind as a bat
• Red as a beet
• Dry as a bone
• Mad as a hatter

13. Physostigma
venosum
Calabar bean

15. Efik People

16. Efik Law
• Trial by ordeal
“A suspected person is given 8 beans ground and
added to water as a drink. If he is guilty, his mouth
shakes and mucus comes from his nose. His
innocence is proved if he lifts his right hand and
then regurgitates” (Simmons 1952)
• Deadly esere
• Administration of the Calabar bean
• First observed by WF Daniell in 1840
• Later described by Freeman 1846 in a
Communication to the Ethnological
Society of Edinburgh

17. Physostigmine or Eserine
First isolated in 1864 by Jobst & Hesse

18. ‘Taxol’
• Pacific Yew tree, Taxus brevifolia, bark
• 1964 activity discovered at NCI
• 1966 paclitaxel isolated
• Mitotic inhibitor
– interferes with normal microtubule growth during cell div
• Used for cancer chemotherapy
– lung, ovarian, breast, head & neck, Kaposi’s sarcoma

19. • 1969
• 1200kg bark -> 28kg crude extract -> 10g pure
• 1975 active in another in vitro assay
• 1977 7000 pounds bark requested to make 600g
• 1978 Mildly active in leukaemic mice
• 1979 Horowitz; unknown mechanism
• involved stabilising of microtubules
• 1980 20,000 pounds of bark needed
• 1982 Animal studies completed

20. • 1984 Phase I trials
• 12,000 pounds for Phase II to go ahead
• 1986 Phase II trials began
• Recognised 60,000 pounds miniumum needed
• Environmental concerns voiced
• 1988
• An effect in melanoma
• RR of 30% refractory ovarian cases
• Annual destruction of 360,000 trees to treat all US cases
• 1989 NCI handed over to BMS
• Agreed to find alternative production pathway
• 1992 BMS given FDA approval & 5yrs marketing rights
• Trademark ‘Taxol’ Generic paclitaxel
• 2000 sales peaked US$1.6 billion
• Now available as generic

21. Alternative production
– 1967-1993 all sourced from Pacific Yew
– Late 1970s synthetic production from petrochemical-
derived starting materials
– 1981 Potier isolated 10-deacetylbaccitin from Taxus
baccata needles
– 1988 published semi-synthetic route
– 1992 Holton patented improved process improving
yield to 80%
– 1995 use of Pacific Yew stopped
– Now plant cell fermentation (PCF) technology used
– Also found in fungi
– Race for synthetic production -> docetaxel

22. Why do we need plants?
1. Source of drug molecules
• Most drugs can be synthesised
• Still more economical to use the plant
Papaver opium -> morphine, codeine (strong medicinal
pain)
Ergot fungus –> ergotamine (headache), ergometrine
(direct action on uterine muscle)

23. Digitalis foxglove -> digoxin
(acts on cardiac muscle)

24. 2. Source of complex molecules that can be
modified to medicinal compounds
• Examples:
Droscera yam: molecule -> steroids
Soya: saponins -> steroids

25. 3. Source of toxic molecules
• To study the way the body responds to their
pharmacological use
• Investigating pharmacological mechanisms
picrotoxin – nerve conduction

26. Morphine:
No better painkiller. Once structure worked out wanted
to improve it. What is required?
Diacetylmorphine (heroin):
OH group -> O-O-diacetyl. Still addictive?
Codeine:
Methylate hydroxyl phenolic; O-Me. 1/5 analgesic
capacity of morphine, useful to suppress cough reflex
Dihydromorphinone:
Reduced =, oxidised 2y alc. Potential analgesic.
4. Source of compounds to use as
templates for designing new drugs

27. Dihydrocodeine:
Me-ether of previous. More powerful than codeine,
less than morphine.
Dextromethorphan:
Good against cough reflex
Is lower ring necessary?
Pentazocin
Phenazocine
Is middle ring needed?
Pethidine
Methadone

28. • 5. Source of novel structures
• these might never be thought of
Catharanthus periwinkle -> vincristine (alkaloid dimer)

29. • 6. Source of plant drugs
• As a powder or extract
• The pure compound is often not isolated because:
» Active ingredient is unknown
» Active ingredient is unstable
» Isolation process is too costly

30. • 250,-500,000 species of higher plants on earth
• <10% investigated and only for one activity
• Huge potential in plant kingdom
Future: intense screening
» Anticancer - NCI
» Antimicrobial
» Antiviral
» Antimalarial
» Insecticidal
» Hypoglycaemic
» Cardiotonic
» Antiprotozoal
» Antifertility - WHO

31. • Screening
– Pharmacological – in vitro testing
– Chemical – certain constituents Eg alkaloids
• Failed screening work
– Incorrect identification of plant material
– Plants exist in chemical races – different
constituents
– Low yield of active compound
– Solubility – have to find correct solvent

32. Future
80% world population rely on natural
remedies
• Westernization of societies
(‘traditional’ knowledge)
• Extermination of species
» conservation, retain gene pools
• Natural resources exhausted
» cultivation, artificial propogation

33. Conclusion
• Natural products very important to
medicine
• Exist in range of structures that one
wouldn’t think of synthesizing
• Can act as templates for new drug
development
• Untapped reservoir of new compounds