S1 L1 Pharma Cog Nosy Introduction

8/6/2019 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

S1 L1 Pharma Cog Nosy Introduction

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