Pharmacognosy I (Part 6)

7/27/2019 Pharmacognosy I (Part 6)

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Glycosides & Tannins


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Glycosides

Glycosides consist of a sugar residue covalentlybound to a different structure called the aglycone.

The sugar residue is in its cyclic form and thepoint of attachment is the hydroxyl group of the

hemiacetal function. The sugar moiety can be joined to the aglycone in

various ways:

1. Oxygen (O-glycoside)2. Sulphur(S-glycoside)

3. Nitrogen (N-glycoside)

4. Carbon (Cglycoside)


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-Glycosides and -glycosides are distinguished

by the configuration of the hemiacetal hydroxyl

group. The majority of naturally-occurring glycosides

are -glycosides.

O-Glycosides can easily be cleaved into sugarand aglycone by hydrolysis with acids or

enzymes.

Almost all plants that contain glycosides alsocontain enzymes that bring about their hydrolysis

(glycosidases).


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Glycosides are usually soluble in water and in

polar organic solvents, whereas aglycones are

normally insoluble or only slightly soluble inwater.

It is often very difficult to isolate intactglycosides because of their polar character.

Many important drugs are glycosides and theirpharmacological effects are largely determined

by the structure of the aglycone.


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The term 'glycoside' is a very general one which

embraces all the many and varied combinations

of sugars and aglycones.

More precise terms are available to describe

particular classes. Some of these terms refer to:

1. the sugar part of the molecule (e.g.glucoside).

2. the aglycone (e.g. anthraquinone).

3. the physical or pharmacological property (e.g.

saponin soap-like, cardiac having an action on

the heart).


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Modern system of naming glycosides using the

termination '-oside' (e.g. sennoside).

Although glycosides form a natural group in that

they all contain a sugar unit, the aglycones are ofsuch varied nature and complexity that glycosides

vary very much in their physical and chemical

properties and in their pharmacological action.


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1. Anthracene glycosides

Anthracene

A number of glycosides in which the aglycones are

anthracene derivatives occur as the pharmacologically

active constituents of several cathartics of plant origin;

e.g. cascara, rhubarb, aloe and senna.

These anthracene glycosides are sometimes referred to as

the anthraquinone glycosides or the anthraglycosides.


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These anthraquinone derivatives are glycosides,

often glucosides or rhamnosides.

The presence of the sugar residue is a prerequisitefor the pharmacological effects.

Anthraquinones are colored substances and many

of them are used technically as dyes e.g. alizarin. Reduced forms of anthraquinones, which exhibit

keto-enol tautomerism, are often encountered.

The anthracene derivatives occur in vegetabledrugs in different forms at different oxidation

levels; like anthraquinones, anthrones, anthranols,

or oxanthrones.


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Interrelationship of anthraquinone derivatives

O

O

O

OH

Anthrone (keto form)

Anthranol (enol form)

Anthraquinone

O

O

Dianthrone

O

H OH

Oxanthrone

A B C

1

2

3

45

6

7

8

9

10

4 H

2 H

2 H

Taut.


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These anthracene compounds occur in these drugs or plant

materials in some cases as the aglycones ofO-glycosides (e.g.

frangulin), and in other cases as the aglycones ofC-glycosides

(e.g. aloin).

Biosynthesis; natural anthraquinones are synthesized either via

the acetate-malonate pathway (like the medicinally important

purgative anthraquinones), or they are derived from shikimate

and mevalonate (like alizarin).

O

O

OH

OH

Alizarin

OHOOH

HO

O

CH3

Frangula emodin


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A. Anthraquinones

Although anthraquinone is not used extensively inmedical practice, it is the starting material for the

preparation of several synthetic laxatives and

represent the basic structure of a number ofimportant laxatives and dyestuffs.

Borntragers testis often used for their detection.

The derivatives of anthraquinone present inpurgative drugs may be dihydroxy phenols such as

chrysophanol, trihydroxy phenols such as emodin

or tetrahydroxy phenols such as carminic acid.


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O

O

Anthraquinone

OH O OH

O

CH3

Chrysophanol

OHOOH

HO

O

CH3

Emodin

HO

OH

OH

O

O

CH3

OH

COOH

O

HO

HO

OH

OH

Carminic Acid


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B. Anthrones & Anthranols

These reduced anthraquinone derivatives occur

either free or combined as glycosides. They are isomeric and one may be partially

converted to the other in solution.

Anthranols are converted upon oxidation intoanthraquinones. Oxidation takes place in the crudedrug during storage especially if powdered.

Schontetens testis often used for anthranols(green fluorescence).

Anthranols and anthrones are the main constituentsof chrysarobin, a mixture of substances.


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OH OH OH

CH3

OH O OH

CH3

Chrysarobin

(1,8-dihydroxy-3-methyl-9-anthrone; 3-methyl-1,8,9-anthracenetriol)


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C. Oxanthrones OH O OH

H OH

These are intermediate products betweenanthraquinones and anthranols.

They give anthraquinones on oxidation with

hydrogen peroxide. An oxanthrone has been reported as a constituent

ofcascara bark.


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D. DianthronesO OH

COOH

COOH

O

-D-glucoseO

-D-glucoseO OH

Sennosides

These are compounds derived from

two anthrone molecules, which may

be identical or different.

They are important aglycones in

species ofCassia,Rheum andRhamnus.

One of the best known is sennoside

derived from two molecules of

glucose and two molecules of rhein-anthrone.

On hydrolysis, sennoside yields the

aglycone sennidin.


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E. Aloin-type or C-glycosides

Aloin (Barbaloin) was obtainedfrom species ofAloe.

It is strongly resistant to normal

acid hydrolysis.

In aloin, the sugar is joined to

aglycone with a direct C-C linkage

(a C-glycoside).

Two aloins (A and B) are knownand arise from the chiral centre at

C-10.

OH O OH

OH

O

HO

OH

OH

HO

Aloin


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2. Saponin glycosides


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A group of plant glycosides known as saponins

share in varying degrees, two commoncharacteristics:

(a) They foam in aqueous solution.

(b) They cause haemolysis of red blood cells.

The aglycones of the saponins are collectivelyreferred to as Sapogenins. The more poisonous

saponins are often called Sapotoxins.


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Plant materials containing saponins have long

been used in many parts of the world for their

detergent properties for example, in Europe, the

root ofSaponaria officinalis (Fam.

Caryophyllaceae)andin South America, the barkofQuillaia saponaria (Fam.Rosaceae). Such

plants contain a high percentage of the glycosides

known as saponins (Latin Sapo, means Soap)

which are characterized by their property of

producing a frothing aqueous solution.


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Properties:

Saponins form colloidal solution in water

(hydrophilic colloids) which froths upon shaking.

These substances modify and lower the surface

tension and therefore foam when shaken. This has

led to their use to increase the foaming of beer.

Practical industrial applications of saponins

include their use in cleaning industrial equipmentand fine fabrics and as powerful emulsifiers of

certain resins, fats and fixed oils.


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In general, they have a bitter, acrid taste anddrugs containing them are usually sternutatory

(causing or producing sneezing) and irritating to themucous membranes of eyes and nose.

Characteristic for all saponins is their ability tocause haemolysis of red blood corpuscles and to

destroy them. When injected into the bloodstream, they are highly toxic.

When taken by mouth, Saponins are

comparatively harmless, being not absorbed fromthe intestinal tract. Sarsaparilla, for example, isrich in saponins but is widely used in thepreparation of nonalcoholic beverages.


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Saponins are toxic especially to cold-bloodedanimals e.g. frogs. Many are used as fish-poisons.

The actual cause of the haemolysis:The red blood cells carry sterols in theirmembranes, and when brought into contact withsaponins, the sterols of the RBCs are precipitatedand the colloidal chemical properties of themembrane are so altered as to give hemoglobinpassage to the surrounding medium.

Saponins have a high molecular weight and theirisolation in a state of purity presents somedifficulties.


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Structure of Saponins:

According to the structure of the aglycone or

sapogenin, two kinds of saponin are recognized:

1. The steroidal type (commonly tetracyclic

triterpenoids, C-27).

2. The triterpenoid type (pentacyclic triterpenoids,

C-30).

Both of these have a glycosidal linkage at C-3

and have a common biosynthetic origin via

mevalonic acid and isoprene units.


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Steroid skeleton3

25

26

27

1

18

19

21

17

Pentacyclic triterpenoid skeleton

23 24

25 26

27

28

29 30

3

1


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A. Steroidal saponins

The steroidal saponins are less widely distributed

in nature than the pentacyclic triterpenoid type.

Steroidal saponins are of great pharmaceutical

importance because of their relationship to

compounds such as the sex hormones, cortisone,

diuretic steroids, vitamin D and the cardiac

glycosides.

Examples: Diosgenin (Dioscorea sylvatica),

Sarsapogenin (Smilax sp.).


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B. Pentacyclic triterpenoid saponins

Triterpenoid saponins my be classified into three

groups represented by -amyrin, -amyrin and lupeol. Examples: Primulagenin (Primula sp.), Quillaiac acid

(Quillaia saponaria) and Glycyrrhetinic acid

(Glycyrrhiza sp.).

E

D

Amyrin Amyrin Lupeol

20

19

1713

14


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3. Coumarin glycosides

O O1

2

3

45

6

7

8

Coumarin

(Benzo--pyrone)

The coumarins are shikimate-derived metabolites.

The majority of the coumarins are oxygenated at position

C7. Coumarins have a limited distribution in the plant

kingdom and have been used to classify plants according

to their presence (chemotaxonomy).


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Coumarins are commonly found in the plant

familiesApiaceae,Rutaceae,Asteraceae and

Fabaceae. Some coumarins are phytoalexinsand are

synthesized de novo by the plant following

infection by a bacterium or fungus.

Phytoalexins:any of a group of compounds

formed in plants in response to fungal infection,

physical damage, chemical injury, or apathogenic process. Phytoalexins inhibit or

destroy the invading agent.


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These phytoalexins are

broadly antimicrobial; for

example, scopoletin is

synthesized by the potato

(Solanum tuberosum)

following fungal infection.

Khellin is an isocoumarin

(chromone) natural product

fromAmmi Visnaga

(Apiaceae) and has activity as

a spasmolytic and vasodilator.

O OHO

H3CO

Scopoletin

O

O

CH3

OCH3

OCH3

O

Khellin


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It has long been known that

animals fed sweet clover

(Melilotus officinalis,

Fabaceae) die from

haemorrhaging. The

poisonous compound

responsible for this adverseeffect was identified as

dicoumarol.

A number of compounds have

been synthesized based on thedicoumarol structure, e.g.

warfarin, which is widely

used as anticoagulant.O O

OH

CH3

O

Warfarin

O O

OH OH

O O

Dicoumarol


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The psoralens are coumarins

that possess a furan ring and

are sometimes known as

furanocoumarins. e.g.psoralen and bergapten.

These compounds may beproduced by the plant as a

protection mechanism against

high doses of sunlight and

some coumarins areformulated into sunscreens

and cosmetics for this

purpose.

OO O

Bergapten

OCH3

OO O

Psoralen


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4. Flavonoid glycosides

Biosynthesis:

flavonoids are products from a cinnamoyl-CoA

(C6C3, precursor from the shikimate pathway)starter unit, with chain extension using three

molecules of malonyl-CoA.

Flavonoids are therefore of mixed biosynthesis,consisting of units derived from both shikimate

and acetate pathways.


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The triketide starter unit undergoes cyclization by

the enzyme chalcone synthase to generate the

chalcone group of flavonoids. Cyclization canthen occur to give a pyranone ring containing

flavanone nucleus, which can either have the C2-

C3 bond oxidized (unsaturated) to give theflavones or be hydroxylated at position C3 of the

pyranone ring to give the flavanonol group of

flavonoids. The flavanonols may then be furtheroxidized to yield the anthocyanins, which

contribute to the brilliant blues of flowers and the

dark colour of red wine.


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The flavonoids contribute to many other colors

found in nature, particularly the yellow and

orange of petals; even the colourless flavonoidsabsorb light in the UV spectrum (due to their

extensive chromophores) and are visible to many

insects. [A chromophoreis the part (or moiety)of a molecule responsible for its color].

It is likely that these compounds have high

ecologicalimportance in nature as colourattractants to insects and birds as an aid to plant

pollination.


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Certain flavonoids also markedly affect the taste

of foods: for example, some are very bitter andastringent such as the flavanone glycoside

naringin, which occurs in the peel of grapefruit

(Citrus paradisi). Interestingly. the closelyrelated compound naringin dihydrochalcone,

which lacks the pyranone ring of naringin, is

exceptionally sweet, being some 1000 timessweeter than table sugar (sucrose).


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the flavonoids have important dietary

significance because, being phenolic compounds,they are strongly antioxidant.

Many disease states are known to be exacerbatedby the presence offree radicals such as

superoxide and hydroxyl, and flavonoids have the

ability to scavenge and effectivelymop up

these

damaging oxidizing species.


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Foods rich in this group have therefore been proposed tobe important in ameliorating diseases such as cancer andheart disease (which can be worsened by oxidation of

low-density lipoprotein); quercetin, a flavonoid presentin many foodstuffs, is a strong antioxidant. Componentsof milk thistle (Silybum marianum), in particularsilybin,are antihepatotoxins; extracts of milk thistle are

generally known as silymarin.

O

OH

OOH

HO

OH

OH

Quercetin

O

O

O

HO

OH O

OH

OCH3

OH

OH

Silybin


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Some action and therapeutic uses of

flavonoids

Many flavonoid containing plants are:

1. Diuretic.

2. Antispasmodic.

3. Diaphoretic.

4. Increase tensile strength of capillary walls.

5. Free radical scavengers.

5 C ti l id


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5. Cyanogenetic glycosides

(Cyanide glycosides)

Cyanogenesis is the ability of certain living

organisms, plants in particular, to produce

hydrocyanic acid (HCN, prussic acid).

Cyanogenesis in plants is a chemical defense

mechanism against organism damaging or feeding

on plant tissues and lead to release of HCN gas,

which is toxic.

They are distributed in over 2000 plant species

belonging to 110 families.


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These compounds, in presence of enzymes such

as -glucosidase, lose their sugar portion to forma cyanohydrin which, in the presence of waterand hydroxynitrile lyase, can undergo hydrolysis

to give benzaldehyde and the highly toxic

hydrogen cyanide (HCN). The sugar portion of the molecule may be a

monosaccharide or a disaccharide such as

gentiobiose or vicianose. If a disaccharide,enzymes present in the plant may bring about

hydrolysis in two stages, as in the case of

amygdalin.

R


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They are derivatives of-hydroxynitrile or 2-hydroxynitrile (cyanohydrins).

In all cases the first sugar attached to the aglycone is-D-glucose.

R1 and R2 are often different residues resulting inpairs of C-2 epimers.

(Epimersare diastereomers that differ in configuration at only oneof their stereogenic centers).

R1

R2

CN

OSugar

M i l id bi h i ll


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Most cyanogenetic glycosides are biosynthetically

derived from the amino acids: valine, leucine, isoleucine,

tyrosine or phenylalanine.

Cyanogenetic glycosides are easy to detect with a strip

of filter paper impregnated with reagents able to give a

color reaction with the hydrocyanic acid released upon

crushing the plant material (e.g., picric acid/sodiumcarbonate or benzidine/cupric acetate).

Although hydrocyanic acid is a violent poison, it is

important to remember that oral intake of cyanogenetic

drugs does not necessarily cause severe intoxication, thisis because the range of dangerous concentrations (0.5-

3.5 mg/kg) can only be achieved by rapid and massive

ingestion of plant parts rich in cyanogenetic glycosides.


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Examples:

1. Amygdalin in bitter almonds (Prunus amygdalus). It is

biosynthetically derived from phenylalanine.2. Linamarin in linseed (Linum usitatissimum). It is

biosynthetically derived from valine.

OHO

HO O

OHO O

OH

HO

HOOH

CN

Amygdalin

CN

OO

HO

OH

HO

OH

Linamarin

CH3

CH3

H


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6. Steroidal cardioactive glycosides

Cardiac glycosides are a group of natural productscharacterized by their specific effect on myocardial

contraction and atrioventricular conduction.

In large doses they are toxic and bring about cardiac

arrest in systole, but in lower doses they are

important drugs in the treatment ofcongestive heart

failure.

They have a diuretic activity. Since, the improvedcirculation tends to improve renal secretion, which

relieves the edema often associated with heart

failure.

Di t ib ti i t


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Distribution in nature

Cardiac glycosides occur in small amounts in

the seeds, leaves, stems, roots or barks of plantsof wide geographical distribution, particularly ofthe Fam.Apocyanaceae (e.g. seeds ofStrophanthus, roots ofApocynum and fruits of

Acokanthera); others are found in theScrophulariaceae (e.g. leaves ofDigitalis sp.),Liliaceae (e.g. scales of the bulbs ofUrginea andConvallaria), andRanunculaceae (Adonis).

Cardiac glycosides are also found in animals onlyin exceptional cases: Bufadienolides occur intoads (Bufo).

St t f l id 18 Lactone ring


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Structure of glycosides

The structure comprise a steroidal aglycone of the

(C23) cardenolide type or of the (C24)bufadienolide type, and a sugar moiety, most

often an oligosaccharide.

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

Lactone ring

O

Sugar moiety

A B

C D

A Structure of the aglycones


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A. Structure of the aglycones

All of the aglycones have in common the classic,

tetracyclic, steroidal nucleus.

The A, B, C and D rings normally have a cis-

trans-cis configuration or less often, a trans-

trans-cis configuration.

Also common to all the aglycones is the presence

of two hydroxyl groups: one is a 3 secondary

alcohol, the other is a 14 tertiary alcohol.

All of the aglycones have a constituent at C-17:

an ,-unsaturated lactone.

O


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The size of the lactone ring distinguishes two groups of

aglycones: the C23 cardenolides with an ,-unsaturated-lactone (= butenolide) and the C24 bufadienolides with

a di-unsaturated -lactone (= pentadienolide).

OOO

1415

16

17

20

21

22

23

1415

16

17

20

21

22

23

24

Lactone ring of

CardenolideLactone ring of

Bufadienolide

B St t f th i t


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B. Structure of the sugar moiety

The sugar moiety is generally linked to the aglyconethrough the hydroxyl group at C-3.

The majority of the saccharides found in cardiacglycosides are highly specific:

1. 2,6-dideoxyhexoses, e.g. D-digitoxose

2. 2,6-dideoxy-3-methylhexoses, e.g. D-diginose

3. 6-deoxyhexoses, e.g. L-rhamnose

4. 6-deoxy-3-methylhexoses, e.g. D-digitalose

5. Hexose, e.g. glucose (when these is a glucose unit, it is alwaysterminal).

The sugars can modify the activity (potency, toxicity),the solubility, the diffusion through membranes, the rateof absorption and transportation of the glycosides.

C St t A ti it R l ti hi (SAR)


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C. Structure-Activity Relationships (SAR)

The cardiac activity is linked to the aglycone.

The sugar moiety does not participate directly in theactivity, but its presence enhances the activity andmodulates it by modifying the polarity of the compound.

The presence of a certain number of structural elements is

required for, or at least favorable, to the activity:1. The lactone at C-17, and it must be in the configuration.

2. The configuration of the rings. The activity is maximizedwhen the A, B, C and D rings are in the cis, trans, cis

configuration. The C and D rings must be cis fused.

3. The substituents. The inversion of the configuration at C-3 diminishes the activity, but 3-deoxy compounds are notcompletely inactive.

O O


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HO

H

H

CH3

H

H

CH3

O

O

HOH

Digitoxigenin

A/B cis - B/C trans - C/D cis

OH

HO

A B

C D

Bi th ti i i


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Biosynthetic origin

Aglycone of the cardiac glycosides are derivedfrom mevalonic acid but the final molecules arise

from a condensation of a C21 steroid with a C2

unit (the source of C-22 and C-23).

Bufadienolides are condensation products of a

C21 steroid and a C3 unit.

Color reactions


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Color reactions

They can be due to the sugars or to the aglycone:

A. Color reactions of the sugars. The only color reactions ofthe sugars that are of interest are those specific to 2-

deoxyhexoses. e.g. Keller-Ki l iani test.

B. Color reactions of the aglycones(steroidal nucleus).

These are positive with any compound containing a

steroidal nucleus including cardenolides or bufadienolide:

1) Antimony trichloride (SbCl3)

2) Liebermann's test (for bufadienolides)


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C. Color reactions of the aglycones(lactone ring).

These are characteristic for cardenolides having a

five-membered lactone ring:

1. Legal's test

2. Raymond's test

3. Kedde's test

4. Baljet's test

Ph l i l i


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Pharmacological properties Cardiac glycosides increase the force and speed of

contraction of the heart. In patients with cardiacinsufficiency, this positive inotropic effect

translates into 1an increase in cardiac output, 2an

increase in cardiac work capacity without anyincrease in oxygen consumption, 3a decrease in

heart rate, and, indirectly, 4a decrease in arterial

resistance. (MOA) The glycosides are thought to

act at the membrane level, by inhibition of theNa-

K ATPase, which would result in an increase of the

intracellular calcium ion concentration.

Therapeutic indications


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Therapeutic indications

Cardiac glycosides are currently indicated for:

1. Cardiac insufficiency with low output (generally

in combination with diuretics), particularly when

there is atrial fibrillation.

2. Supraventricular rhythm abnormalities: to slow

down or decrease atrial fibrillation or flutter.

Examples


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Examples

Strophanthus glycosides

The name Strophanthus is

der ived from the Greek

strophos (a twisted cord or

rope) and anthos (a flower).e.g. Strophanthus kombe

The principle glycosides are:

1.

K-strophanthoside2. K-strophanthin-3. Cymarin

O


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CH

CH3

OH

O

OH

H

H

O

O

Cymarose-D-glucose -D-glucose

Cymarin

K-strophanthin-K-strophanthoside


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Squill glycosides

Urginea maritima(L.)0.1% 2.4% total bufadienolides,15 glycosides

White variety: average 0.2%-0.4%

proscillaridin A, scillaren A,glucoscillaren A (aglycone:scillarenin)

scilliphaeoside, scilliglaucoside

Red variety: < 0.1%

scilliroside and glucoscilliroside(aglycone: scillirosidin);

proscillaridin A and scillaren A asin the white variety


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Pharmacological properties of squill


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Pharmacological properties of squill

White squill:

it is an expectorant, but it also possesses emetic,

cardiotonic (proscillaridin A), and diuretic

properties.

Red squill:

it is used as a rat poison (scilliroside), because

rodents lack the vomiting reflex, which makes

red squill particularly lethal to these animals.


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CH3

-D-glucoseO

CH3

O CH3

O

O

O

H

OH

OH

Scilliroside

(3,6)-6-(Acetyloxy)-3-(-D-glucopyranosyloxy)-8,14-dihydroxybufa-4,20,22-trienolide


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Digitalis glycosides

Several species ofDigitalis yield pharmacologically

active principles. The most important of these species areDigitalis purpurea andDigitalis lanata.

1. Digitalis purpurea folium (Red foxglove leaves)

0.15%0.4% total cardenolides, 30 glycosidesPurpurea glycosides A and B (60%), digitoxin (12%),

gitoxin (10%) and gitaloxin (10%).

2.

Digitalis lanata folium (White foxglove leaves)0.5%1.5% total cardenolides, 60 glycosides

Lanatosides A and C (50%), lanatosides B, D, E aswell as digoxin and digitoxin.


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Digitoxin is a cardiotonic

Digoxin is the most widely


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Digitoxinis a cardiotonicglycoside obtained fromD.

purpurea, D. lanata.

It is the most lipid-soluble ofthe cardiac glycosides used in

therapeutics.

The major pharmacokinetic

parameters for digitoxin

include complete oral

absorption, which

distinguishes it from othercardiac glycosides.

Digitoxin may be indicated in

patients with impaired renal

function.

Digoxinis the most widelyused of the cardiotonic

glycosides, and it is obtained

from the leaves ofD. lanata. It is a highly potent drug and

should be handled with

exceptional care.

Digoxin tablets are 60 to

80% absorbed.

Digoxin is indicated when the

risk of digitalis intoxication is

great, since it is relatively short-

acting and rapidly eliminated

when compared with digitoxin.


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Digitali s purpurea

7 T i


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7. Tannins

Historically, the importance of tannin-containingdrugs is linked to their tanning properties, in

other words their ability to transform fresh hides

into an imputrescible material: leather.

Tannins are "phenolic natural products that

precipitate proteins from their aqueous solutions".

Th f i i h f i f


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The consequence of tanning is the formation of

bonds between the collagen fibers in the hide,

which imparts resistance to water, heat, andabrasion. This capability of tannins to combine

with macromolecules explains why they

precipitate cellulose, pectins, and proteins; italso explains their characteristic astringency

and tartness: by precipitating the glycoproteins

contained in saliva, tannins make the latter lose

its lubricating power.

Most true tanninshave molecular weights

from about 1000 5000.


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Pseudotannins

They are compounds of lower molecular weight

than true tannins and they do not respond to the

goldbeater's skin test.

Examples of drugs containing Pseudotannins are:

Gallic acid: Rhubarb

Catechins: Guarana, Cocoa

Chlorogenic acid: Mate, Coffee

Ipecacuanhic acid:ipecacuanha

OH


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Gallic acid

COOH

OH

OH

HO

Catechin

OHO

OH

OH

OH

OH

Chlorogenic acid

O

O

OH

HO

OHHOOC

OH

OH

Function of tannins in plants


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u ct o o ta s p a ts

1. Tannins are considered thesource of energy

through their oxygen content.

2. They serve as aprotective to the plant (plant

antiseptics).

3. They may havefunction in respiratory activity, i.e.

in the mechanisms of hydrogen transfer in plant

cells.

4. Tannins play an important part in the acceptance

of many foods and beverages by consumers e.g.

tea, cocoa.

Classification of tannins


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Classification of tannins

In higher plants, two groups of tannins are

generally distinguished, which differ by their

structure, as well as their biosynthetic origin:

hydrolysable tannins and condensedtannins.

Hydrolysable tannins

Hydrolysable tannins are esters of a sugar (orrelated polyol) and of a variable number of

phenolic acid molecules.

The sugar is most generally glucose


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The sugar is most generally glucose.

The phenolic acid is eithergallic acid, in the case

ofgallitannins, orEllagic acid, in the case of thetannins conventionally referred to asellagitannins.

Ellagic acid can arise by lactonization of

hexahydroxydiphenic acid (= HHDP) duringchemical hydrolysis of the tannin.

Hydrolysable tanninswere formerly known as

pyrogallol tannins, because on dry distillationgallic acid and similar components are convertedinto pyrogallol.

i i lli id ( 3 4


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Biosynthetically, gallic acid (= 3,4,5-

trihydroxybenzoic acid) arises from the

metabolism of shikimic acid. Examples of drugs containing Hydrolysable

tannins:

Gallitannins: rhubarb, cloves, Chinese galls,Turkish galls, hamamelis, chestnut and maple.

Ellagitannins:pomegranate rind, pomegranate

bark, eucalyptus leaves, and oak bark.

OH OH


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Gallic acid

COOH

OH

OH

HO

OH

OH

HO

Pyrogallol

OH

OH

HO

OH

COOHHO

HOOC

Hexahydroxydiphenic acid

O

O

O

O

OH

OH

HO

Ellagic Acid

Condensed tannins (proanthocyanidins)


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Condensed tannins (proanthocyanidins)

Condensed tannins orproanthocyanidins are

polymeric flavans. They consist offlavan-3-olunits linked together by carbon-carbon bonds,

most often 48 or 46, which result from

coupling between the electrophilic C4 of a

flavanyl unit from a flavan-4-ol or flavan-3,4-diol

and a nucleophilic position (C-8, less commonly

C-6) of another unit, generally a flavan-3-ol.

Unlike hydrolysable tannins, these are not readily

hydrolyzed to simpler molecules and they do not

contain a sugar moiety.

OH OH


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OHO

OH

OH

OH

OH

(+) Catechin (catechol)

OHO

OH

OH

OH

OH

Flavan-3,4-diol structure

OHO

OH

OH

OH

OH

OHO

OH

OH

OH

OH

A dimeric structure

Biosynthetically flavonoids are derived from


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Biosynthetically, flavonoids are derived from

acetate and shikimate pathways.

Condensed tannins occur due to polymerization(condensation) reactions between flavonoids.

The polymers may include up to 50 monomer

units. On treatment with acids or enzymes condensed

tannins are converted into red insoluble

compounds known as phlobaphenes.Phlobaphenes give the characteristic red colour to

many drugs such as red cinnamon bark.

Examples of drugs containing Condensed


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p g gtannins:

Some drugs (e.g. tea, hamamelis leaves and hamamelis

bark) contain both hydrolysable and condensed tannins.

The following are rich in condensed tannins.

(1) Barks:cinnamon, wild cherry, cinchona, willow, acacia,

oak and hamamelis(2) Roots and rhizomes:krameria (rhatany) and male fern

(3) Flowers:lime and hawthorn

(4) Seeds:cocoa, guarana, and kola

(5) Leaves:hamamelis, hawthorn and tea, especially green tea

(6) Extracts and dried juices:catechu, acacia and mangrove

cutches


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Properties and tests of tannins


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Tannins are soluble in water, dilute alkalis, alcohol,

glycerol and acetone, but generally only sparingly

soluble in other organic solvents.

Solutions precipitate heavy metals, alkaloids, glycosides

and gelatin.

With ferric salts, gallitannins and ellagitannins give blue-black precipitates and condensed tannins brownish-green

ones.If a very dilute ferric chloride solution is gradually

added to an aqueous extract of hamamelis leaves (which

contains both types of tannin), a blue colour is produced

which changes to olive-green as more ferric chloride is

added. Other useful tests are the following:

G ldb t ' ki t t


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1. Goldbeater ' s skin test

Soak a small piece of goldbeater's skin in 2%

hydrochloric acid; rinse with distilled water andplace in the solution to be tested for 5 min.

Wash with distilled water and transfer to a 1%

solution of ferrous sulphate. A brown or blackcolour on the skin denotes the presence of

tannins. Goldbeater's skin is a membrane

prepared from the intestine of the ox andbehaves similarly to an untanned hide.

Gelatin test


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2. Gelatin test

Solutions of tannins (about 0.5-1 %) precipitate a

1% solution of gelatin containing 10% sodiumchloride. Gallic acid and other pseudotannins

also precipitate gelatin if the solutions are

sufficiently concentrated.3. Phenazone test

4. Test for catechin

5. Test for chlorogenic acid

Medicinal and biological properties


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The applications of tannin-containing drugs are

limited, and result from their affinity for proteins. Tannin-containing drugs will precipitate protein

and have been used traditionally as styptics and

internally for the protection of inflamed surfacesof mouth and throat.

They act as antidiarrhoeals and have been

employed as antidotes in poisoning by heavymetals, alkaloids and glycosides.


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sumac

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Pharmacognosy I (Part 6)

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