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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