1. Pharmacognosy II (PHG322)1
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2. PHG 322: Course Description
The following subjects will be covered:
1- Plants containing Alkaloids (botanical and chemical character)
Introduction
Examples of medicinally important Alkaloids and their importance as “Lead Compounds” from the following groups:
Phenylalkylamine , Tropolone, Imidazole, Pyridine, Piperidine, Tropane, Quinoline, Isoquinoline, Opium, Indole, Carboline, Purine and Steroidal alkaloids.
2- Marine Derived Drugs
Introduction, Biomedical potential of marine natural products
Biologically active substances from marine source (Anticancer, Antiviral, Antimicrobial, Antiparasitic and Antiinflammatory active compounds).
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3. PHG 322: Course Description
The following subjects will be covered:
3- Plants containing Glycosides (botanical and chemical characters)
Introduction, Examples of medicinally important Glycosides and their importance as a “Lead Compounds” from the following groups:
Cardiac glycosides, Saponins glycosides, Anthracene derivatives, flavonoidal glycosides and related compounds, & Cyanogenic glycosides, thioglycosides and phenylpropan-derivatives.
4- Toxicological Pharmacognosy (Poisonous plants)
Introduction, Poisonous plants, important toxic plants affecting: nervous system, cardiovascular system, gastrointestinal tract, respiratory system.
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4. PHG 322: Course Description
The following subjects will be covered:
5- Herb-Drug interactions
Mechanisms of Drug Interaction with Herbs. Problems Monitoring Herb-Drug Interaction. Herb-Drug Interactions reports: cardiovascular system, central Nervous System, pain Killers and anti-inflammatory drugs
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5. Required Text book Pharmacognosy, Trease and Evans,
ترجمة منصور السعيد و محمد اليحيى، المركز العربي للتعريب والترجمة والنشر – دمشق، 2003
Pharmacognosy and Pharmacobiotechnology, Williams & Wilkins, 1996.
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6. Alkaloids
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7. Deviation from Definition:
Alkaloids, which mean alkali-like substances, are basic nitrogenous heterocyclic compounds of plant origin generally possessing a marked physiological action.
Deviation from Definition:
Some alkaloids are not basic e.g. Colchicine, Piperine, quaternary alkaloids
Few alkaloids contain nitrogen in a non-ring system e.g. Ephedrine, Colchicine. Mescaline
3) Plant origin: Some alkaloids are derived from bacteria, fungi, insects, frogs, animals.
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8. Classification 4- False alkaloids 3- Pseudo alkaloids
1- True alkaloids
- Derived from amino acid.
- Nitrogen atom is a part of
heterocyclic ring.
2- Proto-alkaloids
- Nitrogem atom is not a part
of heterocyclic ring.
3- Pseudo alkaloids
- Not derived from amino acid.
- Nitrogen atom is a part of hetrocyclic ring.
4- False alkaloids
- non alkaloids give false
positive reaction with
alkaloidal reagents.
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9. Distribution and occurrence:
Rare in lower plants.
Dicots are more rich in alkaloids than Monocots.
Families rich in Alkaloids: Apocynaceae, Rubiaceae,
Solanaceae and Papaveracea.
Families free from Alkaloids: Rosaceae, Labiatae
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.
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10. Distribution in Plants
All Parts e.g. Datura.
Barks e.g. Cinchona
Seeds e.g. Nux vomica
Roots e.g. Aconite
Fruits e.g. Black pepper
Leaves e.g. Tobacco
Latex e.g. Opium
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11. Forms of Alkaloids Free bases
Salts with Organic acids e.g. Oxalic, acetic acids
Salts with inorganic acids e.g. HCl, H2SO4
Salts with special acids e.g. Meconic acid in Opium, Quinic acid in Cinchona
Glycosidal form e.g. Solanine in Solanum.
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12. Nomenclature of Alkaloids
Trivial names of alkaloids should terminate with the suffix: (ine)
Their names may be derived from:
Genus name e.g. Atropine from Atropa.
Species name e.g. Cocaine from Coca.
Common name e.g. Ergotamine from Ergot.
Physiological activity e.g. Emetine (emetic).
Discoverer e.g. Pelletierine from Pelletier.
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13. Nomenclature of Alkaloids (Contin..)
Prefixes and suffixes:
These are, usually, added to the name of the parent alkaloid and are used to designate related alkaloids, generally present in the same plant.
Examples are:
Prefixes:
"Nor-" designates N-demethylation or N-demethoxylation, e.g. norpseudoephedrine and nornicotine.
"Apo-" designates dehydration e.g. apomorphine.
"Iso-, pseudo-, neo-, and epi-" indicate different types of isomers.
Suffixes:
"-dine" designates isomerism as quinidine and cinchonidine.
"-ine" indicates, in case of ergot alkaloids, a lower pharmacological activity e.g. ergotaminine is less potent than ergotamine.
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14. Physical Properties 1- Condition: 2- Color:
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.
2- 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.
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15. Physical Properties (Contin..)
3- Solubility:
Both alkaloidal bases and their salts are soluble in alcohol.
Generally, the bases are soluble in organic solvents and insoluble in water.
Salts are usually soluble in water and, insoluble or sparingly soluble in organic solvents.
Exceptions:
Bases soluble in water: caffeine, ephedrine, codeine, colchicine, pilocarpine and quaternary ammonium bases.
Bases insoluble or sparingly soluble in certain organic solvents: morphine in ether, theobromine and theophylline in benzene.
Salts insoluble in water: quinine monosulphate.
Salts soluble in organic solvents: lobeline and apoatropine hydrochlorides are soluble in chloroform.
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16. Physical Properties (Contin..)
4- Isomerization:
Optically active isomers may show different physiological activities.
l-ephedrine is 3.5 times more active than d-ephedrine.
l-ergotamine is 3-4 times more active than d-ergotamine.
d- Tubocurarine is more active than the corresponding l- form.
Quinine (l-form) is antimalarial and its d- isomer quinidine is antiarrythmic.
The racemic (optically inactive) dl-atropine is physiologically active.
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17. Chemical Properties 1- Nitrogen: 2- Basicity:
Primary amines R-NH e.g. Norephedrine
Secondary amines R2-NH e.g. Ephedrine
Tertiary amines R3-N e.g. Atropine
Quaternary ammonium salts R4-N⁺ e.g d-Tubocurarine
2- Basicity:
R2-NH > R-NH2 > R3-N
Saturated hexacyclic amines are more basic than aromatic amines.
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18. Chemical Properties (Contin..) Quaternary ammonium ion
N in alkaloids → in form of amine
Primary amino group
Secondary amino group
Tertiary amino group
Quaternary ammonium ion
e.g.
Norpseudo-ephedrine
Ephedrine
Nicotine
Tubocurarine
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19. Factors influencing the degree of basicity:
Structure of the molecule
Presence & position of other substituents & functional groups
e.g. degree of unsaturation
of heterocyclic ring
Pyridine
Piperidine
Electron
withdrawing gps
Electron
releasing groups
e.g.
carbonyl group
e.g.
alkyl group
Piperidine alkaloids →
more basic than pyridine alkaloids
decrease basicity
increase basicity
unsaturation decreases basicity
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20. Chemical Properties (Contin..)
According to basicity alkaloids are classified into:
Weak bases e.g. Caffeine
Strong bases e.g. Atropine
Amphoteric → due to the presence of acidic group(s)
e.g. Phenolic Alkaloids or Alkaloids with Carboxylic groups
e.g. Morphine e.g. Narceine
Neutral alkaloids e.g. Colchicine
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21. Chemical Properties (Contin..)
3- Oxygen:
Most alkaloids contain Oxygen and are solid in nature e.g. Atropine.
Some alkaloids are free from Oxygen and are mostly liquids e.g. Nicotine, Coniine.
4- Stability:
A- Effect of heat:
Alkaloids are decomposed by heat, except Strychnine and caffeine (sublimable).
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22. Chemical Properties (Contin..)
B- Reaction with acids:
Salt formation.
Dil acids hydrolyze
- Ester Alkaloids e.g. Atropine and Glucoalkaloids e.g Solanine
C- Conc. acids may cause:
Dehydration: e.g Atropine to Apoatropine and Morphine to Apomorphine
Demethoxylation: e.g. Codeine
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23. Chemical Properties (Contin..)
C- Reaction with alkalies:
1- Dil alkalis
They liberate most alkaloids from their salts e.g. NH3.
They may cause isomerization (racemization) of alkaloid e.g. the conversion
of hyoscyamine to atropine.
They also can form salts with alkaloids containing a carboxylic group e.g. narceine.
2- Strong alkalis: such as aqueous NaOH and KOH
They may form salts with phenolic alkaloids.
They hydrolysis Ester alkaloids (e.g. atropine, cocaine and physostigmine) and Amide alkaloids ( colchicines).
They cause opening of lactone ring e.g. Pilocarpine.
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24. Chemical Properties (Contin..)
D- Effect of light and Oxygen:
Some alkaloids are unstable when exposed to light and Oxygen:
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25. Detection and characterization
A- Precipitation by certain reagents
1-  Mayer’s reagent (potassium-mercuric iodide) yellowish-white precipitate.
2-  Dragendorff’s reagent (potassium-bismuth iodide) gives orange red recipitate.
3-  Wagner’s reagent (potassium triiodide) forms red flocculent precipitate.
B- Color reactions with certain reagents
1-  Froehd’s reagent (sulphomolybdic acid)
2-  Marqui’s reagent (formaldehyde + H2SO4)
3-  Mandalin’s reagent (sulphovanadic acid)
4-  Mecke’s reagent (selenic acid + H2SO4)
5-  Erdmann’s reagent (HNO3 + H2SO4)
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26. Extraction, Purification and Isolation of Alkaloids
Method I: The powder is treated with alkalis to liberates the free bases that can then be extracted with water immiscible organic solvents. Method II: The powdered material is extracted with water or aqueous alcohol containing dilute acid. Alkaloids are extracted as their salts together with accompanying soluble impurities. Method III: The powder is extracted with water soluble organic solvents such as MeOH or EtOH which are good solvents for both salts and free bases.
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27. Classification of Alkaloids
Biogenetic.
Based on the biogenetic pathway that form the alkaloids.
Botanical Source.
According to the plant source of alkaloids.
Type of Amines.
Primary, Secondary, Tertiary alkaloids.
Basic Chemical Skeleton
tropane, quinoline, imidazol, isoquinoline, etc… alkaloids.
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28. Basic nucleus or skeletons of alkaloids
Phenylalkylamines alkaloids
e.g. Ephedrine
Pyridine and piperidine alkaloids
e.g. lobeline, nicotine
Tropane alkaloids
e.g. Atropine.
Quinoline alkaloids
e.g. quinine and quinidine
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29. Basic nucleus or skeletons of alkaloids
Isoquinoline alkaloids e.g. papaverine
Phenantheren alkaloids e.g. Morphine
Indole alkaloids e.g. ergometrine
Imidazole alkaloids e.g. pilocarpine
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30. Basic nucleus or skeletons of alkaloids
Purine alkaloids e.g. caffeine
Steroidal alkaloids e.g. Solanum and Veratrum alkaloids
Terpenoid alkaloids e.g. Taxol
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31. Drugs containing pyridine alkaloids
Examples of drugs containing alkaloids
Drugs containing pyridine alkaloids
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32. Classification of Pyridine Alkaloids
Pyridine alkaloids can be classified according to the building nucleus into:
Pyridine nucleus only
Pyridine nucleus another nitrogenous ring
Tetrahydro-pyridine
nucleus
Piperidine
nucleus
Pyridone
nucleus
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33. Classification of Pyridine Alkaloids
Pyridine alkaloids can be classified according to the building nucleus into:
This type of alkaloids could be divided into 4 subgroups and the nucleus of the molecule is one of the following nuclei:
1- Pyridine alone:
e.g. trigonelline
2- Pyridine with other nitrogenous rings (e.g. pyrrol-ring)
e.g. tobacco alkaloids
3- Tetrahydropyridine
e.g. areca alkaloids
4- Pyridone
e.g. ricinine
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34. Drugs containing pyridine alkaloids
Tobaccos
The leaves of the tobacco plant
Nicotiana tabacum (Fam: Solanaceae)
are used for production of Cigarettes.
They are toxic plants which contain
alkaloids, chiefly represented by nicotine.
Other close structurally alkaloids have been
found such as nornicotine, the N-oxidized
derivatives of nicotine, e.g. nicotyrine,
anabasine and anatabine.
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35. Tobacco-alkaloids: Identification 1- Volatile liquid alkaloids
► 4-6% several volatile, non-volatile and crystalline alkaloids:
1- Volatile liquid alkaloids
e.g. nicotine, nor-nicotine, anabasine and anatabine.
2- Non-volatile liquid alkaloids
e.g. nicoteine and nicotyrine
3- Solid-alkaloids
e.g. nicotelline
Identification
1- Nicotine + p-dimethylaminobenzaldehyd + HCl gives
rose-red color.
2- aq. Solution of nicotine + acidic vanillin gives red color.
3- aq. Solution of nicotine + formaldehyde + HNO3 gives red color.
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36. Examples of Tobacco alkaloids
air or light
Colourless or pale yellow oily liquid
brown
Nicotine
non-volatile
liquid
Volatile
liquids
(-)-nicotine (major)
nicoteine
nor-nicotine
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37. Pharmacology: (nicotinic) receptors.
Nicotine possesses a high affinity to the gangionic-cholinergic
(nicotinic) receptors.
So, it stimulates all autonomic ganglia.
It acts on the CNS causing tremors and convulsions.
It also stimulates the respiratory and vomiting centers.
It acts on the smooth muscle of the intestine, by increasing
tone and motor activity.
It acts on the cardiovascular system, by inducing vasoconstriction
and an increase in arterial blood pressure.
In the long run, nicotine is responsible for the genesis of
cardiovascular and pulmonary diseases.
It is used in the form of chewing gum or transdermal system for
relieving the symptoms of withdrawal of cigarettes.
It is also used as insecticide and anthelmintic in veterinary medicine.
It increases incidence of abortion.
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38. Drugs containing Pipiridine alkaloids
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39. 1- Black Pepper dried fruits of Piper nigrum (Fam.
Piperaceae), a perennial plant in
(India and cultivated also in Indonesia,
Sri Lanka and South America).
The pungent taste is due to piperidine
amides (5-10 %).
The chief constituent is piperine
(insecticide), an amide of piperidine
and of piperic acid.
The other amides are piperidines (piperanine, piperettine, piperolein A and Piperolein B), pyrrolidines (piperyline).
Piperidine
Piperine
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40. PHG322, Alakloids1

41. Piperine: Colorless, odorless needles or prisms with burning taste,
insoluble in H2O, soluble in alcohol, chloroform and ether.
Exhibits only weak basicity (no salt with acid).
On hydrolysis, gives piperidine and piperic acid.
Used as stomachic and insecticide.
Has CNS depressant and anticonvulsant effects in rats.
Identification of Piperine:
1- On the addition of Wagner’s reagent, steel blue needle crystals
of piperine periodide are formed.
2- Piperine on treating with platiniumchloride solution gives
orange red needles.
3- Piperine on treating with H2SO4 gives a red color.
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42. 2- Pomegranate The plant is a shrub widespread Punica
granatum (Fam. Punicaceae).
The bark contains % total
alkaloids: (-) pelletierine, isopelletierene,
and N-methylated analogs.
The plant is used as anthelmintic..
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43. 3- Lobelia alkaloids
The dried aerial parts of Lobelia inflata (indian tobacoo).
The major alkaloid is Lobeline.
It is used in the treatment of asthma, chronic bronchitis and in
anti-smoking preparations.
Injection of lobeline hydrochloride is used in the resuscitation of
newborn infants.
Caution: Toxic doses of the herb has a paralytic effect.
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