This document provides information about cardiac glycosides, which are glycosides that have effects on heart function. It discusses their sources, structures, properties, methods of identification and examples. The key points are: - Cardiac glycosides are found in plants and contain an aglycone steroid part and a sugar part. - They have effects on the heart muscle by increasing its contractility and slowing heart rate. - Major sources include Digitalis, Strophanthus, Nerium and Thevetia plants. - They contain lactone rings which can be 5 or 6-membered, and are identified using chemical tests on plant extracts.

1. GLYCOSIDES
Presented by
Mrs. Pooja Khanpara
M Pharm (Pharmacognosy)
Assistant Professor
APIP, Jamnagar 1

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Some glycosides have antibacterial activity, so they
protect the plants from bacteria and diseases.
Bitter almond
bacteria
HCNhydrolysisAmygdallin
enzyme
kill

6. .’;’;;’
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12. STASS OTTO METHOD
Powdered plant material (Crude Drug)
Continuous Hot Extraction with alcohol (Soxhlet)
Collect the Extract
Add Leadacetate to precipitate tannins
Filter and pass H2S gas
Filter and subject to fractional crystalization, distillation or chromatography
Pure Glycoside

12

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Class or Type Examples
Phenyl glycosides Arbutin (bearberry), Glucovanilline (Vannila Spp)
Anthraquinone Sennoside (Senna)
Flavone Hespiridin (Orange and lemon)
Cyanogenic Visnagin (Ammi visnaga)
Glucoalkaloids Solasodine (Solanum)
Steroid (Cardiac) Digitoxigenin (Digitalis)
Saponins Dioscorin (Dioscorea)
Coumarin Umbelliferone (Asafoetida)

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Class or Type Chemical tests
Anthraquinone 1. Borntrager’s test
2. Modified Borntrager’s test
Flavone (Flavonoids) Shinoda test
Cyanogenic Grignard’s test
Steroid (Cardiac) 1. Legal’s test
2. Baljet’s test
3. Keller-Killiani’s test
Saponins 1. Foam test
2. Haemolytic test
Coumarin U.V. light test

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Example of glycoside Effects/Uses/Application
Sennoside, aloin laxative
Digitoxin, strophanthin Cardiotonic
Sinigrin (Black mustard) GIT irritant
Salicin (Salix Spp.) Anti-rheumatic
Glycyrrhetinic acid Anti peptic ulcer
Hespiridin Capillary fragility
Methyl salicylate (Gaultheria) analgesic

16. CARDIAC GLYCOSIDES OR
STEROLS
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INTRODUCTION
• The genins(aglycon part) of all cardiac glycosides are steroidal in
nature, that act as cardiotonic agents.
• They are characterized by their highly specific action cardiac
muscle, increasing tone, excitability and contractility of this muscle,
thus allowing the weakened heart to function more efficiently.
O
R
OH
CH3
Sugar
Lactone ring
1
2
3
4
5
10
6
7
8
9
11
12
13
14
15
16
17
cyclopentanoperhudrophenanthrene

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 All cardio active glycosides are characterized by the
following structural features:
1. The presence of β-OH at position C-3, which is always involved
in a glycosidic linkage to a mono, di, tri, OR tetra saccharide.
2. The presence of another β-OH group at C-14.
3. The presence of unsaturated 5 or 6- membered lactone ring at
position C-17, also in the β configuration.
4. The A/B ring junction is usually (cis), while the B/C ring
junction is always (trans) and the C/D ring junction is in all
cases (cis).
5. Additional OH groups may be present at C-5, C-11 and C-16.
O
R
OH
CH3
Sugar
Lactone ring
1
2
3
4
5
10
6
7
8
9
11
12
13
14
15
16
17

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Cardiac glycosides that α-β unsaturated 5-membered lactose ring
in position C-17 are known as cardenolides. These are
represented by the digitalis and straphanthus group and shows
slowing and strengthening effect on failing heart.
Digitalis glycosides contain angular methyl group at C-10, while
strophanthus glycoside are characterized by presence of either an
aldehydic (CHO) or primary alcoholic (C`H2OH) group at C-10.
O
R
OH
CH3OH
Sugar
1
2
3
4
5
10
6
7
8
9
11
12
13
14
15
16
17
O O

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O
R
OH
CH3OH
Sugar
1
2
3
4
5
10
6
7
8
9
11
12
13
14
15
16
17
O O
Cardenolides
Digitalis glycosides R=CH3
Strophanthus glycosides R=CHO OR CH2OH
Cardiac agents that have doubly unsaturated 6-membered lactone
ring in position C-17 are referred to as Bufadienolides.
This group includes the squill glycosides and the toad venom,
Bufotoxin.
• ‘Bufo’ derived from toad genus, ‘adien’ denotes double bond
while ‘olide’ denotes Lactone ring.

21.  They are found in higher plants.
 They are abundant in family apocyanaceae, asclepedaceae,
Ranunculaceae, sterculiaceae, leguminosae etc.
 They are also found in monocots like liliaceae family. E.g. squill.
 They are also found in frogs (African toads).
 These two glycosides are distinguished according to the presence of 5 or
6 membered lactone ring.
 Those with five membered lactone ring are cardenolides e.g.
digitoxigenin, digoxigenin, gitaloxigenin, gitoxigenin, strophanthidin.
 Those with six membered lactone ring are bufadienolide e.g. scillaren A
 Maximum plants contains cardenolides.
Modern use:
 to treat congestive heart failure (dropsy).
 for treatment of atrial fibrillation and flutter.
 aglycone structure important for activity. 21

22. General properties of Cardiac Glycosides :
 Amorphous powder
 Bitter taste
 Solubility in H2O
 Insolubility in Organic solvents
 Very toxic compounds
 Odorless
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23. PHYSICAL AND CHEMICAL PROPERTIES OF
CARDIAC GLYCOSIDES:
 Solubility:
 Glycosides are soluble in water and alcohols.
 Increase number of sugars increase water solubility.
 Aglycones soluble in CHCl3 and EtOAc.
 Stability:
 Acid hydrolysis:
 Split sugars from the aglycone first.
 Enzymatic hydrolysis:
 Split sugars stepwise starting from the terminal sugar.
 Elevated temperature:
 Cause dehydration by removal of C-14 OH group to give
inactive anhydro-form
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24. CLASSIFICATIONS OF CARDIAC GLYCOSIDES:
According to their therapeutic effects:
CHF(congestive heart failure) and cardiac muscle
stimulators such as:
 Digitalis glycosides: digoxin, digitoxin, gitoxin (Fox
glove leaves).
 Ouabain: Strophanthus gratus seeds.
 K-strophanthin: Strophanthus kombe seeds.
 Scillaren A,B which isolated from red and white
Squill bulbs.
 Convolloside:Convallaria majalis: Lily of the
Valley. 24

25. According to the type of lactone ring:
1. Cardenolide (one double bond, lactone ring) :
Has five member lactone ring (unsaturated) attached at C17 B
position of steroidal nucleus.
Examples:
Digitalis glycosides:
Digoxin
Digitoxin
Gitoxin
Strophanthus gratus glycoside :
Oubain
Strophanthus Kombe glycoside :
K- strophanthin
2. Bufadienolide: (contain two double bonds, lactone ring):
Has six member ( unsaturated ) lactone ring attached at C-17
alpha – position
Example:
Squill bulb glycoside
Scillaren
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26. Nomenclature :
 The cardiac glycosides occur mainly in plants from which the
names have been derived.
 Digitalis purpurea,
 Digitalis lanata,
 Strophanthus kombe are the major sources of the
cardiac glycosides.
 Aglycone moiety:
 The term 'genin' at the end refers to only the aglycone portion
(without the sugar).
 The aglycone portion of cardiac glycosides is more important
than the glycone portion.
Aglycone part has steroidal nucleus
cyclopentanoperhudrophenanthrene
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Sugar moiety(glycone) :
The glycosides usually contain 3 to 4 sugars attached at
C-3 OH.
The sugars most commonly used include L-rhamnose, D-
glucose, D-digitoxose, D-digitalose, D-digginose.
Beside Glucose and Rhamnose they usually contain
deoxysugars.
These sugars predominantly exist in the cardiac
glycosides in the β-conformation.
Digitoxose
Digitose

28. STRUCTURE:
THESE are composed of two structural features :
the sugar (glycone) moiety and
the non-sugar (aglycone - steroid) moieties.
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32. CHEMICAL IDENTIFICATION:
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 General test for steroids:
1. Liebermann’s test: compound + chloroform +equal amt. of
acetic anhydride + Few drops of conc. H2SO4
Reddish violet Green
 Test for Deoxysugars:
1. Keller-Kiliani’s Test: powder drug boil with 10 ml alcohol
for 2 min. Filter it add 10 ml water, 0.5 ml lead
acetate sol. Shake well & filtrate treated with chloroform
residue treated with glacial acetic acid cool & add 2
drop of FeCl3 + 2 ml conc. H2SO4 on the wall of the tube
Acetic acid layer acquire Bluish-green colour
(Digitalis)
Acetic acid layer acquire Red colour (Squill)

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 Test for 5-membered lactone ring:
1. Legal’s test:
Drug is boil with little pyridine + few drops of Na nitroprusside
+ made alkaline(NaOH) deep pink to red colour.
2. Baljet test:Substance + sod. Picrate +alkaline  yellow orange
colour
3. Kedde’s test : Drug + 1 drop of alcohol + 2 drop of 3,5
dinitrobenzoic acid (Kedde’s reagent A) + NaOH (Kedde’s
reagent B)  violet(purple) colour.
4. Raymond Tests:
Substance + 0.1 ml 1% sol. Of dinitro benzene in methanol + 2-
3- drops of NaOH  voilet then change in blue colour.

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 Xanthydrol test (deoxysugar):
Substance +xanthydrol reagent in acetic acid + 1% Hcl 
Red color
 Salkowaski test:
drug chloroform sol. + conc. H2SO4  chloroform layer
produce Red color
 Tollen’s test:
extract + mixture of pyridine & ammonial silver nitrate 
form of silver mirror on wall of test tube
 Antimony trichloride test:
drug solution heated with antimony trichloride and
trichloroacetic acid  blue or violate color

35. SOURCES
 Scrophulariaceae
 Digitalis purpurea leaves (foxglove)
 Digitalis lanata leaves – white flowers
 Apocyanaceae
 Strophanthus vine seeds – Africa
 Liliceae
 Urginea bulbs (squill) – Europe, India
 Convallaria leaves (lily of the valley) – also
produces a volatile oil perfume
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OH
cholestrol
NADPH 2
O2
OH
OH
OH
NADPH 2O2
OH
O
O
H
O
PREGNENLONEO
O
PROGESTRONE
O
O
5 -Pregnane 3,2 dione
O
PREGNENALONE OH
OH
O
DIOL
OH
OH
O
OH
TRIOL
acetyl CoA
OH
OH
O
O
12 - hydroxylation
oxalo acetyl CoA
bufalin
C - 2 - unit
strophanthadin
16 - hydroxylation
OH
OH
O
O
H
H
OH
OH
O
O
H
OH
digitoxigenin
gitoxigenin

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40. MICROSCOPY
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41.  Chemical constituents:
 It is required to contain at least 0.3% of total
cardinolides calculated as digitoxin.
 Purpurea glycoside A & B
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49. DIGITALIS:
 Scrophulariaceae family:
 Digitalis Thapsi leaf – Yellowish green
lenceolate with decurrent lamina &
crenate margin.
 Spain & Itali
 Digitalis lanata leaf – white, woolly
foxglove, Grecian foxglove (sessile)
 Holland, USA
 Digitalis lutea (yellow) leaf – Straw
foxglove,
 USA, Europe
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4. S. Hispidus
5. S. sarmentotusd
6. S. emini
7. Kickxia Africana

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 Morphology of Strophanthus seed:
 Color: externally light fawn color with distinct greenish
tinge
 Odour: heavy when seed are crushed and moist
 Taste: Bitter
 Shape : ovale lanceolate ovoid, flatened and obtusely edged
 Size ; 7-20 mm long, 4 mm wide 2 mm thick

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 Morphology of Nerium leaves:
 Color: dark dusty green
 Odour: aromatic sweet
 Taste: Bitter
 Shape : narrow lanceolate
 Size ; 5-21 cm long & 1-3.5 cm broad
 Cultivation & collection:
 Loamy or soft soil, clay containing clay or natural mineral

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 Morphology of thevetia seed:
 Color: green to greyish black
 Odour: none
 Taste: Bitter & produce numbness when chewed
 Shape : oblong
 Size ; upto 7 cm