pharmacognosy i (part 6)
TRANSCRIPT
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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