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Introduction to alkaloids
Pharmacognosy II – third Year Alkaloids 1
Mohammed N. Sabir January 2020
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Lecture outlines…
▪ Background▪ Occurrence in nature▪ Physicochemical properties▪ Extraction and identification▪ Nomenclature▪ Classification▪ Role in plants▪ Pharmacologic activities▪ Biosynthesis▪ Ornithine derived alkaloids
▪ Pyridine-piperidine-pyrrolidine derivatives▪ Arecoline▪ Nicotine
Background, historical, sociological, and medical
aspects…
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Occurrence in nature…
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Specific alkaloids are confined to specific
plant families:-
1-Morphine in Papaveraceae.
2-Colchicine in Liliaceae.
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Exceptions…
3-Nicotine, which is found in several widely scattered plant
families, is an exception to this rule.
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4-Ergot alkaloids found in the fungus
(Claviceps purpurea and certain Ipomoea
species, Convolvulaceae)
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-Some alkaloids are found in animals, ex. (dendrobatid
alkaloids in Frogs, and pyrrolizidine alkaloids in insects)
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https://www.liveandinvestoverseas.com/news/beware-central-americas-poisonous-frogs/10
http://www.arterrarium.com/species11
https://animaldiversity.org/accounts/Oophaga_pumilio/12
https://phys.org/news/2014-12-poison-frog-compounds-ants.html13
-Alkaloids may occur in various parts of the plant; in seeds
(physostigmine, areca), underground parts (sanguinarine),
rhizomes and roots (ipecac, hydrastis), barks (cinchona).
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Physicochemical properties of alkaloids,
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- The basicity of the alkaloids varies according to the
location of the amine.
- The quaternary amines are water soluble.
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Extraction of alkaloids…
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Identification of alkaloids…
Precipitation tests
1-Mayer ’s reagent.
2-Wagner’s reagent.
3-Tannic acid solution.
4-Hager’s reagent.
5-Dragendorff’s reagents.
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Nomenclature of alkaloids…
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Ex:- Opium alkaloids are sometimes called "phenanthrenes",
or by the plants or animals they were isolated from.
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Classification of alkaloids…
Alkaloids are classified by their common molecular precursors
(basic chemical structures from which they are derived), based
on the enzymatic biosynthesis used to construct the molecule.
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Pyridine Piperidine Pyrrolidine Tropane Quinoline
Isoquinoline Indole Imidazole Purine 22
Importance to plants…
1- For protection (poisonous agents).
2- End products of detoxification reactions.
3- Regulatory growth factors.
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Importance to plants…
4- Reserve substances.
5- Byproducts of metabolism.
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Examples on the pharmacologic activities of
alkaloids…
• Morphine and Codeine are narcotic analgesics.
• Strychnine and Brucine are CNS stimulants.
• Atropine is an anticholinergic agent.
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Example on the pharmacologic activities of
alkaloids…
• Physostigmine and Pilocarpine are
parasympathomimetic agents.
• Ephedrine is adrenergic agonist.
• Reserpine causes rapid drop in blood pressure
(used in essential hypertension) and as
antipsychotic.26
Example on the pharmacologic activities of alkaloids…
• Vincristine and Vinblastine are anticancers.
• Ergot alkaloids are vasoconstrictors (used in
migraine), and uterine muscle convulsant (used in
uterine bleeding).
• Colchicine is used for treatment of gout.
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Biosynthesis…
All alkaloids are derived from amino acids, mainly
(phenyl alanine, tyrosine, tryptophan, histidine,
anthranilic acid, lysine, and ornithine)
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Common amino acids utilized for alkaloids’ biosynthesis
Biosynthesis…
The general reaction includes (decarboxylation and
transamination) to yield the corresponding amine or
aldehyde.
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-These can react to form a Schiff base which, in turn,
reacts with a carbanion in a Mannich-type
condensation.
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The general reactions of alkaloid biosynthesis
- CO2COOHR CH2NH2R CHNH2
α-amino acid R'
+ -H2ORN H C3
Schiff baseCOOH
transaminationR' CHOR' CHNH2
H- CO2
α-amino acidR'
CHRNH
+
H C H
R''
CarbanionR'
CH
R''RNH
Alkaloid32
1 Alkaloid derived from Ornithine
L-Ornithine is none-protein amino acid forming part of
the urea cycle in animals.
Plants33
-Ornithine contains both δ- and α-amino groups and
incorporates into alkaloid structures along with the carbon
chain, except for the carbonyl group.
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-Thus ornithine supplies a C4N building block to the alkaloid
principally as a pyrrolidine ring system, but also as a part of the
tropane alkaloids.
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1.1 Pyridine-Piperidine-Pyrrolidine alkaloids
Divided into 3 subgroups:
•Piperidine includes (Lobeline from Lobelia).
•Derivatives of nicotinic acid, including Arecoline from Areca.
•Derivatives of both pyridine and pyrrolidine includes Nicotine
from Tobacco.
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The biosynthesis of Pyridine-Piperidine alkaloids
H2N H NH2
COOH
L-Ornithine
Ornithine
decarboxylase H2N NH2
Putrescine
S-Adenosylmethionine
Putrescine
N-m
ethyltransferaseH2N NHCH3
N-methylputrescine
HCNHCH3O
N-Methylaminobutanal
N
CH3
N-Methylpyrrolinium Ion
NH
HH
C
OHO
N
CH3
N
N
CH3
C
OOH
H
H
H
- CO2
- 2 HN
NH
CH3
(-) Nicotine
N
COOH
Nicotinic acid
N
COOH
COOH
Quinolinic acid
N
COOH
COOH
HOCOOH
H2C
CHCOOH
H2N
+
CH2OH
HOHC
CH2
OP
Glyceraldehyde-3-phosphate
Aspartic Acid Biosynthesis of Nicotine
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Areca
Areca nut, or betel nut is the dried
ripe seed of (Areca catechu L.
Arecaceae).
The fruit is a nut containing single seed with
thin seed coat. The fruit is boiled in water
with lime, and then dried.
38http://www.homeopathyandmore.com/forum/viewtopic.php?t=256.
India is the major producer of areca, and its production
is consumed domestically almost.
Areca is mixed with lime and chewed as a CNS
stimulant.
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In pharmaceuticals, the dried betel nut is used as anthelminthic
in veterinary practice and employed as a vermicide and
taeniafuge.
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The stimulant action of arecoline is attributed to its
agonistic actions on M1, M2, M3 parasympathetic
receptors in brain.
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-Areca contains arecoline (arecaidine methyl ester).
-The total alkaloid content (TAC) can reach 0.45%.
-Arecoline is the most abundant and psychologically most active
alkaloid.
-It is a liquid occurring to the extent of about 0.2%.
-Areca extract also contains tannins (15%), lipids, volatile oils,
and gum.
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43http://findmeacure.com/2008/02/22/betel-nut-bengali-supari/
Nicotine
Is a pyridine-pyrrolidine alkaloid obtained from the dried leaves
of tobacco plant (Nicotiana tabacum L., N. rustica, Solanaceae).
The leaves contains 0.6-0.9% nicotine and less amount of
nornicotine.
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Major alkaloids found in tobacco leaves
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Nicotine is a colorless-pale yellow, very
hygroscopic, oily, volatile liquid with
unpleasant, pungent odor and a sharp,
burning, persistent taste.
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Nicotine is a ganglionic (nicotinic) cholinergic-receptor (nChr)
agonist.
Chronic use of nicotine may result in psychologic and physical
dependence.
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Nicotine stimulates the reward center and drug-
reinforcement behavior in the brain.
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Pharmacologic actions on the…
- Brain
- CVS
- Kidneys
- Liver
- Metabolism
- Cancer
- Pregnancy
- Blood50
Green tobacco sickness
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https://www.who.int/tobacco/healthwarningsdatabase/tobacco_large_Africa_health_effects_01/en/
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Nitrosamine and cancer…
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Cytochrome-
P450
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Nitrosamine and lung cancer
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https://seas.yale.edu/news-events/news/nitrosamine-carcinogens-also-swim-chlorinated-pools
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https://link.springer.com/article/10.1007/s10911-017-9381-z
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https://www.mdpi.com/2072-6694/6/2/1138/htm
As a temporary aid for the cigarette smoking cessation, the drug
is available in transdermal systems, and it is also available bound
to an ion exchange resin in a chewing gum base.
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Nicotinamide (niacinamide) or vitamin B3…
Used for niacin deficiency and pellagra.
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Nicotinamide is also used for hyperlipidemia and topically for the
treatment of acne.
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REVIEW OF THE LECTURE…
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THANKS FOR THE LISTENING…
ANY QUESTIONS?
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https://www.123rf.com/photo_14877018_tobacco-leaf-on-white-background.html
