Cardiac glycosides are steroid compounds found in several plants that increase the force of contraction of the heart muscle. They increase cardiac contractility and output without increasing oxygen consumption or heart rate. Digitalis purpurea and Digitalis lanata are sources of medically important cardiac glycosides like digoxin and digitoxin. These glycosides have an aglycone steroid nucleus and sugars attached. They are used to treat congestive heart failure.

2.  Drugs having the cardiac ionotropic
property increase in force of contraction
of heart muscles.
 They increase the myocardial contractility and
improves cardiac output without proportionate
increase in Oxygen consumption
 Do not increase the heart rate.
 Digitalis is the genus name for the family
of the plants that provide most of the
medically useful cardiac glycosides -
Digoxin

3.  Cardenolides and Bufadienolides
 Digitalis purpurea – Digitoxin, Gitoxin and
Gitalin
 Digitalis lanata - Digitoxin, Gitoxin and
Digoxin
 Strophanthus gratus – Ouabin
 Thevetia nerifolia – Thevetin
 Convallaria majalis – Convallotoxin
 Bufo vulgris - Bufotoxin

4. Digitalis purpurea Digitalis lanata
Strophanthus gratus

5. Urginea maritima Thevetia
nerifolia
Convallaria majalis

6.  All Cardiac glycosides
aglycone (genin) part
(active pharmacologically)
sugar (glucose or digitoxose)
attached at Carbon 3 of
nucleus
 Aglycone : Steroid ring
(cyclopentanoperhydrophena
nthrene ring) and lactone
ring attached at 17th position

7. Cardio-active Glycosides
•Group of steroidal glycosides act as cardiotonic agent.
•They increase tone, excitability and contractility of
cardiac muscles.
General properties of Cardiac Glycosides :
Amorphous powder
Bitter taste
Solubility in H2O
Insolubility in Organic solvents
Very toxic compounds
Odorless
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8.  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.
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9.  Acts on Failing Heart:
 Inability of the heart to pump sufficient blood to meet
the metabolic demands of the body
 Reduced efficiency of the heart as a pump

10. 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. 10

11. 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 11

12. 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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13. 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
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14. STRUCTURE:
These are composed of two structural features :
the sugar (glycone) moiety and
the non-sugar (aglycone - steroid) moieties.
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15. The R group at the 17-position defines the class of cardiac
glycoside.
Two classes have been observed in Nature:
1. cardenolides and
2. bufadienolides .
The cardenolides have an unsaturated butyrolactone ring
While the bufadienolides have an a-pyrone ring.
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16.  Steroidal nucleus must be present.
 3b-OH group involved in glycosidic linkage.
 14b-OH group at C-14.
 A/B ring junction cis
 B/C ring junction trans
 C/D ring junction cis
 Additional oH groups at C-5, C-11 and C-16 may be
present.
 The presence of lactone ring
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17. 17

18.  Scrophulariaceae family:
 foxglove - biennial flowering plants
 cases of poisoning rare
 natural emetic if eaten in excess
 Digitalis purpurea leaf – purple, British
 Digitalis Tablets B.P.
 Tincture of Digitalis B.P.
 commercially grown Holland, E. Europe
 Digitalis lanata leaf – white,
Mediterranean
 used for manufacture of pure glycosides
 i.e. digoxin, lanatoside C
 commericially produced Holland, Equador, USA
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19.  Digitalis consists of the
dried leaves of Digitalis
purpurea.
 It is required to contain
at least 0.3% of total
cardinolides calculated
as digitoxin.
 Parts Used: Leaves
 Habitat: Native to
Western Europe.
Although the plant is
cultivated, wild plants
are thought to be
superior.
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20.  Glycosides
 purpurea glycoside A
 purpurea glycoside B
 Glucogitaloxin
 Steroid cardenolides
 contains 30 glycosides, 6 main ones
 At C-3 of the genin: a linear chain of 3 digitoxose sugar
moieties terminated by glucose.
 On drying: enzyme degradation takes place  loss of the terminal
glucose. Produces
 Digitoxin
 Gitoxin
 Gitaloxin
 also contains anthraquinone glycosides
 Saponins
 Sopogenins
 Flavonoids
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21.  compounds belong to
cardenolide series
 5 membered lactone ring
 approx 96 compounds
 [1930-1950 Stroll
worked on structures]
R1 R2 Names 1y 2y
H H digitoxigenin A A digitoxin
H OH gitoxigenin B B gitoxin
OH H digoxigenin C C digoxin
OH OH diginatigenin D D diginatin
H formylester gitaloxigenin E E gitaloxin
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*
* Acetyl group
confers crystalline
properties - makes
compounds more
easily isolated

22. Some cardioactive glycosides from D.lanata:
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23.  sugar found on primary glycosides of D.lanata.
 glucose on the end of a chain of O-linked digitoxose
sugars at C3.
 expect about 10 compounds from D.lanata
 important ones:
 Digoxin “Lanoxin” – Wellcome – 0.25 μg white tablet
 Digitoxin “Digitalin” 0.25 μg small pink tablet
 Lanatoside “Cedilanid” 0.10 μg – less well absorbed but
used for rapid digitalisation
 Others not marketed, used experimentally 23

24.  They are Cardiotonics used to treat Congestive heart
failure(CHF).
 They increase force of contraction of cardiac muscles without
increase oxygen consumption.
 Increase cardiac output.
 The diastolic phase last longer so decrease heart rate.
 Have diuretic effect due to increase amount of blood passing
through the kidney. 24

25.  General test for steroids:
 Liebermann’s test:
 Glycoside in acetic anhydride + Few drops of conc. H2SO4
Reddish violet Green
 Test for Deoxysugars:
 Keller-Kiliani’s Test:
 Glycoside in acetic anhydride containing traces of FeCl3 +
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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26.  Test for 5-membered lactone ring:
 Legal’s test:
 Cardenolide in pyridine + Na nitroprusside + NaOH
deep red colour.
 Kedde’s test :
 Cardenolide+ 3,5 dinitrobenzoic acid (Kedde’s reagent A)
+ NaOH (Kedde’s reagent B)  violet colour.
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