s1 l1 pharma cog nosy introduction
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S1 L1 Introduction to
Pharmacognosy
Anna Drew
with slide contribution from Bob Hoffman
& grateful acknowledgement for inspirational teaching received at theSchool of Pharmacy, University of London
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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 Beethovens physician
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Naturally occurring substances havinga 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
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Pharmacognosy is related to:
Botany
Ethnobotany
Marine biology
Microbiology
Herbal medicine
Chemistry (phytochemistry)
Pharmacology
Pharmaceutics
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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
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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
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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
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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.
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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)
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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?
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Quinine
Cinchona bark, South American tree
Used by Incas; dried bark ground and mixedwith wine
First used in Rome in 1631
Extracted 1820
Large scale use 1850
Chemical synthesis 1944
Actual tree remains the most economic source
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Belladonna -> atropine
Anticholinergic
syndrome:
Hot as hell
Blind as a bat
Red as a beet
Dry as a bone
Mad as a hatter
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Physostigmavenosum
Calabar bean
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Efik People
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Efik Law
Trial by ordealA suspected person is given 8 beans ground and
added to water as a drink. If he is guilty, his mouthshakes and mucus comes from his nose. His
innocence is proved if he lifts his right hand andthen 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 EthnologicalSociety of Edinburgh
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Physostigmine or Eserine
First isolated in 1864 by Jobst & Hesse
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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, Kaposis sarcoma
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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
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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
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Alternative production
1967-1993 all sourced from Pacific Yew
Late 1970s synthetic production from petrochemical-derived starting materials
1981 Potier isolated 10-deacetylbaccitin from Taxusbaccata needles
1988 published semi-synthetic route
1992 Holton patented improved process improvingyield to 80%
1995 use of Pacific Yew stopped Now plant cell fermentation (PCF) technology used
Also found in fungi
Race for synthetic production -> docetaxel
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Why do we need plants?
1. Source of drug molecules
Most drugs can be synthesised
Still more economical to use the plant
Papaveropium -> morphine, codeine (strong medicinalpain)
Ergotfungus > ergotamine (headache), ergometrine(direct action on uterine muscle)
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Digitalis foxglove -> digoxin(acts on cardiac muscle)
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2. Source of complex molecules that can bemodified to medicinal compounds
Examples:
Droscera yam: molecule -> steroids
Soya: saponins -> steroids
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3. Source of toxic molecules
To study the way the body responds to their
pharmacological use
Investigating pharmacological mechanisms
picrotoxin nerve conduction
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Morphine:
No better painkiller. Once structure worked out wantedto improve it. What is required?
Diacetylmorphine (heroin):
OH group -> O-O-diacetyl. Still addictive?
Codeine:
Methylate hydroxyl phenolic; O-Me. 1/5 analgesiccapacity of morphine, useful to suppress cough reflex
Dihydromorphinone:
Reduced =, oxidised 2y alc. Potential analgesic.
4. Source of compounds to use as templatesfor designing new drugs
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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
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5. Source of novel structures
these might never be thought of
Catharanthus periwinkle -> vincristine (alkaloid dimer)
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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
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250,-500,000 species of higher plants on earth
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Screening
Pharmacological in vitro testing
Chemical certain constituents Eg alkaloids
Failed screening work
Incorrect identification of plant material
Plants exist in chemical races differentconstituents
Low yield of active compound Solubility have to find correct solvent
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Future
80% world population rely on naturalremedies
Westernization of societies(traditional knowledge)
Extermination of species conservation, retain gene pools
Natural resources exhausted cultivation, artificial propogation
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Conclusion
Natural products very important tomedicine
Exist in range of structures that onewouldnt think of synthesizing
Can act as templates for new drugdevelopment
Untapped reservoir of new compounds
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