Transcript Introduction to Pharmacognosy

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
• ‘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
Naturally occurring substances having
a medicinal action:
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Surgical dressings prepared from natural fibres
Flavourings and suspending agents
Disintegrants
Filtering and support media
• Other associated fields:
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Poisonous and hallucinogenic plants
Raw materials for production of oral contraceptives
Allergens
Herbicides and insecticides
Pharmacognosy is related to:
– Botany
– Ethnobotany
– Marine biology
– Microbiology
– Herbal medicine
– Chemistry (phytochemistry)
– Pharmacology
– Pharmaceutics
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
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
CLASS
SUBCLASS
Angiospermae (Angiosperms)
Plants which produce flowers
Gymnospermae (Gymnosperms)
Plants which don't produce flowers
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
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.
Example
• Linnaeus (1707-1778), Swedish biologist
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Division
Class
Subclass
Order
Suborder
Family
Subfamily
Tribe
Genus
Species
Varieties
Angiospermae
Dicotyledoneae
Sympetalae
Tubiflorae
Verbenineae
Labiatae (Lamiaceae)
Stachydoideae
Satureieae
Mentha
Mentha piperita Linnaeus (peppermint)
Mentha piperita var. officinalis Sole
(White Peppermint); Mentha piperita var.
vulgaris Sole (Black Peppermint)
Contribution of plants to
medicine and pharmacy
• 18th century drugs plant based
• 19th century a range of drugs was isolated:
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1805 morphine
1817 emetine
1819 strychnine
1820 quinine
• Famous plants/plant drugs?
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
Belladonna -> atropine
Anticholinergic
syndrome:
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Hot as hell
Blind as a bat
Red as a beet
Dry as a bone
Mad as a hatter
Physostigma
venosum
Calabar bean
Efik People
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
Physostigmine or Eserine
First isolated in 1864 by Jobst & Hesse
‘Taxol’
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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
• 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
• 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
Alternative production
– 1967-1993 all sourced from Pacific Yew
– Late 1970s synthetic production from petrochemicalderived 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
Why do we need plants?
1. Source of drug molecules
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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)
Digitalis foxglove -> digoxin
(acts on cardiac muscle)
2. Source of complex molecules that can be
modified to medicinal compounds
• Examples:
Droscera yam: molecule -> steroids
Soya: saponins -> steroids
3. Source of toxic molecules
• To study the way the body responds to their
pharmacological use
• Investigating pharmacological mechanisms
picrotoxin – nerve conduction
4. Source of compounds to use as templates
for designing new drugs
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.
Dihydrocodeine:
Me-ether of previous. More powerful than codeine,
less than morphine.
Dextromethorphan:
Good against cough reflex
Is lower ring necessary?
Is middle ring needed?
Pentazocin
Pethidine
Phenazocine
Methadone
• 5. Source of novel structures
• these might never be thought of
Catharanthus periwinkle -> vincristine (alkaloid dimer)
• 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
• 250,-500,000 species of higher plants on earth
• <10% investigated and only for one activity
• Huge potential in plant kingdom
Future: intense screening
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Anticancer - NCI
Antimicrobial
Antiviral
Antimalarial
Insecticidal
Hypoglycaemic
Cardiotonic
Antiprotozoal
Antifertility - WHO
• 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
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
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