ALKALOIDS

Dr. Adnan Amin

Assistant Professor
Chairman
Fabruary19, 2018

D e p a r t m e n t o f P h a r m a c o g n o s y, G o m a l U n I v e r s I t y, D e r a I s m a I l K h a n
 Introduction

Cultivation

Overview Chemistry

Identification

Uses
 Introduction

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 ALKALOIDS
Alk = alkali (basic properties), oid = (Like)

• Mainly produced by plants (above 300 plant families and above 10,000 different
types.) (seed bearing)
• About 25 % of higher plants have these molecules
• Also produced by bacteria, fungi and animals.
• Amino acids are precursors
• Alkaloids are a group of physiologically active naturally occurring compounds that
mainly contain nitrogen atom as a part of cyclic system in addition to C and H.

• In addition they also have Sulphur, Chlorine, Phosphorous and Oxygen

• Mainly having basic properties, in some case neutral or weekly acidic
• A highly important class of compounds associated with a number of Pharmacological
Activities.
• Bitter in taste Friedrich Sertürner,
isolated morphine
from opium

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 Function in Plants
• They may act as protective against insects and herbivores due to their bitterness
and toxicity.
• They are, in certain cases, the final products of detoxification (waste products).
• Source of nitrogen in case of nitrogen deficiency.
• They, sometimes, act as growth regulators in certain metabolic systems.
• They may be utilized as a source of energy in case of deficiency in
carbon dioxide assimilation.

Physical Properties
I- Condition:
Most alkaloids are crystalline solids.
Few alkaloids are amorphous solids e.g. emetine.
Some are liquids that are either: Volatile e.g. nicotine and coniine, or Non-volatile e.g.
pilocarpine and hyoscine.
II- Color:
The majority of alkaloids are colorless but some are colored e.g.: Colchicine and berberine are
yellow, Canadine is orange,
The salts of sanguinarine are copper-red.
III- Solubility:
Both alkaloidal bases and their salts are soluble in alcohol.
Generally, the bases are soluble in organic solvents and insoluble in water

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Pharmacological properties

• Antimalarial (e.g. quinine),

• Antiasthma (e.g. ephedrine),
• Anticancer (e.g. homoharringtonine) ,
• Cholinomimetic(e.g. galantamine),
• Vasodilatory (e.g. vincamine),
• Antiarrhythmic (e.g. quinidine),
• Analgesic (e.g. morphine),
• Antibacterial (e.g. chelerythrine),
• Antihyperglycemic activities (e.g. piperine).
• Stimulant activities (e.g. cocaine, caffeine, nicotine, theobromine),.

Toxicity

Alkaloids can be toxic too (e.g. atropine, tubocurarine, strychnine)

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 Identification tests

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 BIOSYNTHESIS
How nitrogen gets into a structure
Nitrogen Fixation is the process by which atmospheric nitrogen (N2) is captured by
certain organisms and converted into NH3, a form of nitrogen
that can be used by all organisms.

Atmospheric nitrogen Nitrogen Fixation Amino Acids

Alkaloids
N2

• Position of nitrogen is very important

• It can be within and outside the ring
• It should be within the ring for a nice activity
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 Biosynthesis
• The amino acids that most often serve as alkaloidal precursors include
pheylalanine, tyrosine, tryptophan, histidine, anthranilic acid, lysine and ornithine.
• The general reactions include the de-caboxylation and transamination of the amino
acids to yield a corresponding amine or aldehyde.
• These an react to form a Schiff base which inturn can react with a carbanion in
Mannich type condensation-

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 Numbering systems
Related to typical class of compounds
Trivial names should end by "ine".

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 Classification
There are many systems of classification of alkaloids-
Most common classification is as follows-
A. True alkaloid: These contain nitrogen in a heterocyclic ring. They are derived from
amino acids and normally occur in plants. E.g. Morphine
Bitter in taste, white in colour
Water soluble
Toxic, show a wide range of physiological activity and
Precursors are L- ornithine, L-lysine etc
B. Protoalkaloids These contain nitrogen in a heterocyclic ring. They are derived
from amino acids and normally occur in plants eg. Ephedrine

C. Pseudoalkaloids These are not derived from amino acid precursors and
are usually basic in nature. e.g. purine alkaloids Nitrogen comes from transamination
reactions. So some indirect AA pathways are producing them

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 Chemical Classification
Nature of basic chemical structure,
1. Atypical or proto or non-heterocyclic alkaloid:
Atypical alkaloids are those which contain nitrogen atom in form of amine in the
branched chain of the structure. they are also called biological amines.

1. Typical or heterocyclic alkaloid:

These contain nitrogen in a cyclic ring of the molecular structure and all basic
properties of alkaloids. These are as follows-
i. Pyrrole- e.g. proline

ii. Pyrrolidine- e.g. Hygrine

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 i. Pyridine- e.g. caffine

ii. Pyperidine- e.g. Quinine

i. Tropane e.g. Atropine

i. IsoQuinoline e.g. Noscapine

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 Extraction
Based On the properties, alkaloid can be isolated from the plant materials:
1. Alkaloid form salt with aqueous mineral acid which when treated with base free
alkaloid is liberated.
2. Free alkaloids are soluble in organic solvent where as the alkaloidal salt soluble
in water.

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 ISOQUINOLINE ALKALOIDS

• Double carbon ring and one nitrogen

• CNS stimulants, GIT irritants, Neurological effects
• Sedative and hypnotic effects
• Toxic to animals

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 OPIUM ‫افیون‬
Plant details (small plant)
Dried juice Obtained from unripe capsule
Plant height is 15 cm

Biological Source
Papaver somniferum (Papaveraceae)
Synonyms
Crude opium, Afim, Post

Geographical source
Afghanistan, India, China, Pakistan

Morphology
• Milky/ exudate
• Dark brown/raddish
• Characteristic smell
• Bitter taste
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Collection and cultivation
• Seeds are sown in April (under License)
• Capsule in June –July
• Unripe (green) capsule are given incisions
in mid day or evening.
• Knife have edges on it only to give longitudinal cuts
• Hit only lax tube don’t cut the capsule
• Milky latex comes, that becomes gummy
• 2 or 3 times cut(Single capsule)
• Removed by brushing
• Collection and drying

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Chemical tests

Chemistry
• 35 different alkaloids, whereas 10-16% is Morphine
• Other include Codeine, Narcotine, Thebane,
• Main are Benzyl Isoquinoline, Thalide Isoquinoline type

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 USES
• Norcotic, Sedative
• Analgesic
• In cough preparations
• Seed used as food and salad dressing

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 IPECAC
Plant details (Shrub)
Roots and rhizomes

Biological Source
Cephalelis ipecacuanha (Rubiaceae)
Synonyms
ipecacuanha, golden root, Rio ipecac,
Brazilian ipecac

Geographical source
Native to Brazil, also in Malaysia, Nicaragua, India

Morphology
• Dark gary, annulated, 5 -15cm
• Fracture is dense
• Characteristic smell
• Bitter taste
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Collection and cultivation
• Low growing shrub
• Grows mainly in forest and sandy areas
• Grown by stem/ root cutting
• Roots/ rhizomes are harvested from 2.5years
Old plant
• Plant is dug out
• Roots are removed and dried

Chemical tests

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 Chemistry
Ipecac’s major constituents are the alkaloids emetine and cephaline. The roots also
contain tannins, calcium oxalate and small amounts of anthraquinone glycosides

USES
• Emetic after poisoning
• It is also used to treat bronchitis associated with croup in children, a severe kind of
diarrhea (amoebic dysentery), and cancer.
• Ipecac is also used as an expectorant to thin mucous and make coughing easier.
Small doses are used to improve appetite.
• Health professionals sometimes give ipecac by IV (intravenously) for hepatitis and
pockets of infection (abscesses).
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 ALKALOIDAL AMINES

• One or more carbon rings and one nitrogen on side chain

• Bronchodilator, Anti allergic, anti spasmotic, Vasoconstriction
• Typical example is mescaline, ephedrine, Colchicine

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 EPHEDRA ‫ چیوا‬، ‫اسمانیہ‬
Plant details (Shrub)
Evergreen shrub, Arial parts

Biological Source
Ephedra gerardiana (Ephedraceae)

Synonyms
Ma Huang

Geographical source
Pakistan, China, Nepal, India

Morphology
• Woody stem, Grey or green in colour
• Aromatic odour
• Bitter taste

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Collection and cultivation
• evergreen shrub 0.6-2m
• Cannot grow in shade
• Can tolerate drought
• Cultivation by seeds, then seedlings in winter
• Green Twigs are collected in autumn

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 MICROSCOPY

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 Chemistry
• Major constituents are the alkaloids ephedrine, pseudoephedrine, nor
pseudoephedrine.
• Some Tanins, saponins, flavonoids etc

USES
• Anti allergic, antispasmodic, antiasthematic
• Cough suppressant
• Decongestant
• Antirheumatoid arthritis

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 COLCHICUM ‫سورنجان‬
Plant details (Herb)
seeds

Biological Source
Colchicul autumnale (Lilaceae)

Synonyms
Meadow Saffron, Colquico, Colchicum seeds

Geographical source
Europe, Germany, Spain, Turkey

Morphology
• Darkbrown/black in colour
• 2-3mm in length
• odourless
• Bitter taste

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Collection and cultivation
• Seeds are sown in summer
• Cannot grow in shade
• Slow growth, takes 18 months
• Seedling are processed further
• Seedling take 4-5 years to reach flowering
• Capsular fruits in spring
• dried and seeds are removed by sifting

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 Chemistry
• Major constituent is poisonous alkaloid Colchicin, demecolcin present.
• Resins, fixed oil, glucose etc.

USES
• Corm(underground part) and seeds are analgesic
• Emetic, antirheumatic
• To treat leukemia

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 PURINE BASES

• Two carbon rings with four Nitrogen

• Basic structure is same as that of adenine(a nitrogenous base), found
in DNA, RNA and ATP
• CNS stimulants, relaxing impact on bronchial smooth muscles
• Diuretic
• Typical examples are Tea , coffee

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 TEA
Plant details (evergreen shrub)
Leaves

Biological Source
Thea sinensis (Theaceae)

Synonyms
Chaay, Tea, Black tea

Geographical source
India, Srilanka, Japan, Ceryleon

Morphology
• Green in colour that become brown upon roasting
• Typical odour
• Taste bitter

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Collection and cultivation
• Evergreen shrub, 4 x 2.5m
• Slow grower, mainly on hilly areas
• Soil PH 5-7, annual rain fall 70-310cm, temp 14-27C
• Cultivation by Seedlings
• Seedling need 4-12years to produce seeds
• Leaves are collected and dried.
• The processed and a typical aroma develops

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 TEA PROCESSING

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 Chemistry
• Major constituents are Caffeine, theobromine, theophyline etc
• Proteins, waxes and volatile oil etc.

USES
• Stimulant, astringent, diuretic

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 COFFEE
Plant details (a small tree upto 5 m)
Seeds

Biological Source
Caffea arabica (Rubiaceae)

Synonyms
Coffee beans, coffee seeds, Brazilian coffee

Geographical source
India, Brazil, Ethopia, Maxico etc

Morphology
• Fruit is red, 1.5cm long
• Seeds are two, 8.5-12.5mm, greenish
• Typical odour
• Taste bitter

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Collection and cultivation
• A small tree(shrub) plant upto 5 m
• Grown by seeds, grafting, budding etc
• Average life is 30-40 years(Upto 100years)
• Fruits mature in 8 months from flowers
• Red fruits are mainly important
• Seeds are collected from 6-8 years old plant
• Ripe berries collected, and dried in air/oven

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 Chemistry
• Major constituents is Caffeine (2-3%).
• Proteins, waxes and volatile oil etc.

USES
• Stimulant, diuretic
• Flavoring agent
• Snake bite, coma
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 PURIDINE-PIPERIDINE TYPE ALKLAOIDS
• Six membered ring system, five Carbons and one N
• Colourless, inflammable, toxic liquid\
• Miscible with water and organic solvents
• Highly reactive N

• Piperidines are derived from pyridine

• Pepper like aroma
• Soluble in water and organic solvents
• Act as crystal intermediates to make various N containing compounds

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 ARECA NUT
Plant details (Tree)
Seeds

Biological Source
Areca catechu (Palmaceae)

Synonyms
Senna Areca, Supari, Semina Areca

Geographical source
India, Srilanka, Malaya, China etc etc

Morphology
• Seeds 2.5cm
• Brown in colour, very hard
• Cheese like odour
• Acrid taste

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Collection and cultivation
• A small tree
• Grown by seeds
• Heavy rain fall, temperature 15-38C
• Seeds are collected from 25-50 years old plant
• Boiled in water with Lime and exported

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 Chemistry
• Major constituents is Arecoline, Guvacine, Arecolidine
• Fatty acids like palmitic acid, stearic acid, lauric acid etc

USES
• Antheminthic, Vermifuge in dogs
• Nerve tonic
• MAY CAUSE CANCER
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 TOBACCO
Plant details (Herb)
Very old history, Herbs that is smoked
Leaves

Biological Source
Nicotiana tobacum (Solanaceae)

Synonyms
Tambako, Tobbaco, Taco folia

Geographical source
India, Srilanka, Pakistan, China Brazil etc

Morphology

• 60-80cm in length
• Green, slight yellow
• Characteristic odour
• Bitter taste
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Collection and cultivation
• Cultivation by seeds
• Warm climate and well fertile soil
• Heavy rain fall, temperature 15-38C
• Flowering tops are cut to boost growth
• Leaves are collected from 90 days old plant

Chemistry
• Nicotine
• After smoke, Nictotine is converted to pridine, fufurol, Carbon
monoxide, hydrocyanic acid etc

USES
• Sedative, diuretic, expectorant
• Antiseptic
• Stimulatory effect on heart.
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 ‫جنگلی سنبل‬ Lobelia
Plant details (Herb)
Erect biennial herb
Leaves/arial parts

Biological Source
Lobelia inflata (lobeliaceae)

Synonyms
Indian tobacco, herba lobelia,
Asthma weed

Geographical source
India, United states, Canada

Morphology

• Green, slightly blue, slight yellow

• Irritating, unpleasant odour
• burning taste
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Collection and cultivation
• 1-2 feet in height
• Cultivation by seeds in march to April
• Warm climate and well fertile soil
• In August/September, when capsular fruit
get inflate
• Arial parts are collected and dried

Chemistry
• Lobeline
• Lebelidine, lobelinidine, Isolobeline

USES
• Expectorant, antiasthematic
• Epilepsy, Tetnus, tonsilitus
• Respiratory stimulant, asphyxsia in newborn
•
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To discontinue the smoking habit
 STEROIDAL ALKLAOIDS

• Cyclopentanophenanthrene with one N

• C21 or C24
• Sugar containg steroidal alkaloidal glycosides
• Pepper like aroma
• Soluble in water and organic solvents
• Act as crystal intermediates to make various N containing compounds

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 ‫ أعشاب سامة‬- ‫فیراترم‬
VERATRUM
Plant details (perennial Herb)
Rhizome, roots

Biological Source
Veratrum viride (Liliaceae)

Synonyms
American hellebore,Green hellebore
Indian poke

Geographical source
United states, Canada, Georgia

Morphology

• 3-8cm x 2.5cm rhizome,

• Small roots 8 cm long, wrinkled
• Odourless, taste bitter
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Collection and cultivation
• A perennial herb
• Cultivation by seeds
• Roots and rhizomes are dug in autumn
• Washed and cleaned, sliced
• Marketed

Chemistry
• Jervine, pseudojervine, rubijervine, cavidine
• Protovertrine A, B

USES
• Antihypertensive,
• Convulsions, Mania
• Insecticidal
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 TROPANE ALKLAOIDS
• 8 Azabicyclo octane nucleus
• Tropane derivatives, That is composed of Pyrolidine and piperidine rings
• Solanaceae, Erythroxylaceae and Convolaceae

• Cleopatra used Night shade and Henbane on slaves to know about using these
to commit suicide(Very painful death=her conclusion)
• Toxic, deaths in kids
• Anticholinergic, diuretic, antinflmmatory

(Pyrilidine) (Piperidine)

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 ‫مکو‬ Belladona
Plant details (perennial herbious plant)
Fruits leaves, stems

Biological Source
Atropa Belladona (Solanaceae)

Synonyms
Belladona leaves, deadly nightshade
Deaths herb, poison black cherry

Geographical source
United states, Canada, Germany, India

Morphology

• Leaves 5-20 cm long , green in colour

• Flowers blackish shade, five petals
• Fruit pale yellow, black, numerous seeds
• Odourless, taste sweet
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Collection and cultivation
• A perennial herbicious plant
• Cultivation by seeds
• Seedlings are used for cultivation
• Maturation in June

Chemistry
• Hyoscyamine, Atropine, Belladonine
• Flavonoids like rutin, quercetin, Kaempferol
• Scopoletin

USES
• Peptic ulcer, digestive disorders
• Anticholinergic properties, removes spasm
• Balladona plaster, stiffness of muscles etc
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 STRAMONIUM ‫دھتورا‬
Plant details (bushy Herb)
Leaves and flowering tops

Biological Source
Datura stromonium
Datura Metel (Solanaceae)

Synonyms
Thorns apple leaves, Jamestown weed
Stinkweed, etc
Geographical source
Europe, India, Asia, South Africa

Morphology

• Leaves heart shaped, outer corolla 5 teeth, inner 9

to 10
• Roots white in colour
• Leaves green, 8-25cm long
• Bitter taste, characteristic odour
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Collection and cultivation
• 1.5 m tall bushy herb
• grows at waste places
• Cultivation by seeds in spring
• Seedlings are used for cultivation
• Maturation in August
• Leaves and tops are collected and dried

Chemistry
• Hyoscyamine, hyoscine(scopolamine)
• Atropine, albumin(Protein)
• Flavonoids like rutin, quercetin, Kaempferol,
Crysiens
• Various steroidal alkaloids

USES
• Narcotic, Antispasmotic,
• Anticholinergic properties, removes spasm in asthma
• For treatment of Prakinsons disease etc
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 HYOSCYAMUS ‫نرجہ‬

Plant details (Bienial Herb)

Leaves(seeds also)

Biological Source
Hyoscymus niger (Solanaceae)

Synonyms
Hog’s ben, Henben, Jupiters ben
Stinkweed, Hyoscyamus niger
Geographical source
Europe, India, Asia,

Morphology

• Leaves green in colour, 9-10 inches

• Pungent taste, nauseous odour

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Collection and cultivation
• 3-4 feet in height
• Cultivation by seeds in spring
• Growth is too slow
• Flowering in first year
• Leaves are collected in June from 2nd year plant
• Dried and stored

Chemistry
• Hyoscine (scopolamine), Hyoscine
• Atropine, albumin(Protein)
• Flavonoids like Rutin, quercetin,
Kaempferol, Crysiens
• Various steroidal alkaloids

Uses
• Narcotic, Antispasmodic
• Henban oil for Massage relieves pain
• Anticholinergic properties, removes spasm in asthma
• For treatment of Parkinson's disease etc
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 QUINOLINE ALKLAOIDS
• A double carbon ring containing one nitrogen
• Cinchona (Rubiaceae)

• Antimalarial, Analgesic, Antipyratic

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 CINCHONA
Plant details (Tree)
Bark, root

Biological Source
Cinchona calisaya (Rubiaceae)

Synonyms
Jesuit’s bark, Peruvian bark,
cinchona bark
Geographical source
Bolivia, Peru, India, Indonesia

Morphology

• Bark is yellow to brown, short fracture

• bitter taste, distinct odour

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Collection and cultivation
• 5-10 feet in height
• Cultivation by seeds, seedlings
• 1.5 years old plant is transferred to field
• Bark is collected from 6 years old plant
• Collection till 9 years old plant
• Dried and stored

Chemistry
• Above 30 alklaoids have reported
• Quinine, quinidine,
• Cinchonine, cinchonidine
• Quinic acid

Quinine
Quinidine
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 Microscopy

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 Uses

• Antimalarial, Analgesic, Antipyratic

• Rheumatoid arthritis

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 INDOLE ALKLAOIDS
• Indole is an aromatic heterocyclic organic compound with formula C8H7N.
• It has a bicyclic structure, consisting of a six-membered benzene ring fused to
• A five-membered pyrrole ring.
• Naturally found in various plant
• Main component of parfumes
• A coulrless crystalline solid
• Indole structure elucidated by Baeyer in 1866.

Vasoconstrictor, Abortifacient, Lessens post partum haemorrages

Analgesic, Antinflmmatory

ERGOTISM Fits/ Convulsions/Nervous contrictions

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 ERGOT
Plant details (Dried scrotium of fungus)
Fungus

Biological Source
Claveceps purpura (Claviceptaceae)
Secale cerele(Poaceae) = Rye plant

Synonyms
Ergot of rye, ergot, Spurred rye

Geographical source
Czechoslovovakia, Hungary, France, India,
Pakistan etc
Morphology

• Sclerotium size in 1-4 cm, 2-7mm broad

• Dark violet to black in colour,
• Odour is characteristic, unpleasant odour

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Collection and cultivation
3 stages

1. Sphacelia / Honey dew stage/A sexual stage

2. Sclerotium stage Sexual stage
3. Ascospore stage

Flowering season, rye plant infection, spread of fungus

By spore
Taken to ovary, penetration into ovary via enzyme
Hyphea formation, Whit e mass, Sphacelia
Also a sweet yellow, viscous syrup is produced called Honey Dew
From ends of hyphae conidiospores (A sexual) are formed
Taken by birds

Now, hyphae penetrate deep, replace parenchyma of plant ovary

Go to a resting(Sclerotium) stage
During summer , the sclerotium increase in size and projects out
Collected

If not collected, they fell on the soil, grown in next spring, produce projections
Called stromata. Each stromata having pockets called Peritheca
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 LIFE CYCLE

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 • Each peritheca has sacs that have eight escospores, that facilitate infection

Chemistry
• Ergotamine, Ergonovine
• Ergotoxin, Ergometrine
• Lysergic acid

Uses
• Vasoconstrictor, Abortifacient,
• Lessens post partum haemorrhages
• Analgesic, Antinflmmatory

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 RAUWOLFIA
Plant details (root)
An evergreen shrub

Biological Source
Rauwolfia serpentina (Apocynaceae)

Synonyms
Sarpagandha, Indian snake root

Geographical source
Indonesia, Burma, Thailand India

Morphology

• Root size in 2-4 cm, 5-22mm broad

• brown in colour,
• Slight, bitter odour

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Collection and cultivation
• Altitude of 1200-1300m, 10-40C temp
• Cultivation by seeds, stem cutting
• 2-5 years old plant
• In Oct-November
• Dried and marketed

Chemistry
• Reserpine, Rescinamine,
• Rescidine, deserpidine etc
• Ajmaline, Ajmalicin, Isoajmaline (AJMAL
DAWAKHANA)
• Serpentine, Rohimbine

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 Uses
• Antihypertensive,
• For treatment of cardiac arrhythmias
• Tranquilizer effects

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 NUX VOMICA
Plant details (tree)
Seeds

Biological Source
Strychnos nux vomica (Loganiaceae)

Synonyms
Kuchla, Poison nuts, kaukar button
Vomit Nut, dog’s button

Geographical source
Australia, Bengal India, Ceryleon

Morphology

• Disc like seeds, with small hairs

• 10-30mm length, 3-5mm thick
• Very hard, no odour, bitter taste

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 Collection and cultivation
• A tall tree upto 12m in height
• Ripe fruits are collected in November, yellow
brown berries
• Epicarp is removed and seeds are washed

Chemistry

• Strychnine, Brucine, loganine, vomicine

• Traces of copper
• Strychnine is toxic and located ate central
pat of endosperm
• Endosperm walls have glucose etc
• Outer part has Brucine, bitter standard

• Serpentine, Rohimbine

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 Uses
• Emetic…?????
• increase appetite
• Effects on spinal cord, improves movements
• Improves functions of various senses
• Helps in cases of cardiac failure
• TOXIC
Poison, respiratory failure,

Chemical test
• Add H2SO4 and Ammonium vanadate to central part pink colour
• Add nitric acid to out part yellow colour

Strychnine

Brucine

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Questions