These are an important class of naturally occurring drugs whose actions include both beneficial and toxic effects on the heart. Plant glycosides with specific action on the heart are known as cardiac glycosides. The main cardiac glycosides are cardenolides found in plants like foxglove and bufadienolides found in toad skin. They work by inhibiting the sodium-potassium ATPase pump in cardiac muscle cells, increasing calcium levels and strengthening heart contractions. Common uses of cardiac glycosides include treatment of congestive heart failure and cardiac arrhythmias.

2.  Organic natural compounds present in a lot of plants and some animals, these
compounds upon hydrolysis give one or more sugars (glycone) moieties and
non sugar (aglycone) moieties
 Glycoside=sugar group+ non-sugar group
 (aglycone or genin)
 Glycosidic linkage is formed between –OH group of sugar and –H group of
non-sugar moieties OR other sugar with loss of water molecule
 glycoside=glycone{---o---}aglycone+Water
 Sugar in glycosides is mostly beta-D glucose but other sugars like galactose,
mannose, rhamnose, digitoxose can present.
 Glycosides can be alpha or beta but plants contains only beta glycosides
 Therapeutic effect of glycosides is only due to aglycone part only and sugar
moiety facilitate absorption of glycoside, transportation of aglycone to site of
action .

3.  Classification based on type of aglycone in glycoside
 Anthraquinone or anthracene glycoside
 Sterols or cardiac glycoside
 Saponin glycoside
 Cyanogenic glycoside
 Isothiocynate glycoside
 Coumarins and furanocoumarins
 Aldehyde glycoside
 phenol glycoside
 Steroidal
 Miscellaneous glycosides

4. classification based on type of linkage between glycone
and aglycone
 Linkage between –OH group of glycone and –H group of
RADICALS LIKE –CH,-OH,-SH,-NH of aglycone.
 Glycoside is named by perfix like
 C-glycoside,-sugar linked to carbon atom of aglycone
 N-glycoside,- sugar linked to nitrogen atom of aglycone
 O-glycoside,- sugar linked to oxygen atom of aglycone
 S- glycoside- sugar linked to sulfur atom of aglycone
classification based on there use
 Cathartics, cardio tonics, analgesics, anti-rheumatics, anti- ulcer
etc

5.  These are an important class of naturally occurring drugs whose actions
include both beneficial and toxic effects on the heart.
 Plant glycosides with specific action on heart.
 Historical use:
 to assassinate people, arrow poisons
 Historical sources:
 South American toad skins, African plant extracts
Modern uses
 To treat congestive heart failure
 For treatment of atrial fibrillation and flutter.
 Aglycone structure important for activity.
 Group of steroidal glycosides act as cardiotonic agent.
 They increase tone, excitability and contractility of cardiac muscles.
 General properties of Cardiac Glycosides :
1. Amorphous powder 2. Bitter taste 3. Solubility in H2O
4. Insolubility in Organic solvents 5.Very toxic compounds 6. Odourless

6.  Solubility:
 Glycosides are soluble in water and alcohols.
 Increase number of sugars increase water solubility.
 Aglycones soluble in CHCl3 and EtOAc.
 cardiac glycosides is a small group of plant glycosides act directly on
the heart muscle.
 These include (but are not limited to cardiac glycosides or
cardenolides)
 Cardenolides are steroidal glycosides
 exert a slowing and strengthening effect on the failing cardiac muscle.
 According to their therapeutic effects:
 CHF(congestive heart failure) and cardiac muscle stimulators such as:
 Digitalis glycosides: digoxin, digitoxin, gitoxin (Foxglove leaves).
 Ouabain: Strophanthus gratus seeds.
 K-strophanthin: Strophanthus kombe seeds.
 Scillaren A,B which isolated from red and white Squill bulbs.

7. 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
Bufadienolide: (contain two double bonds, lactone ring):
Has six member ( unsaturated ) lactone ring attached at C-17 alpha position
Example: Squill bulb glycoside: Scillaren
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

8.  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
 Beside Glucose and Rhamnose they usually contain deoxysugars
 These sugars predominantly exist in the cardiac glycosides in the
β-conformation.
 Structure:
 These are composed of two structural features :
 the sugar (glycone) moiety and
 the non-sugar (aglycone - steroid) moieties.
 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.

10.  STRUCTURE FEATURES:
 Steroidal nucleus must be present.
 3-OH group involved in glycosidic linkage.
 14-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

11. General test for steroids:
 Liebermann’s test:
 Glycoside in acetic anhydride + Few drops of conc. H2SO4
 Reddish violet turns to 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)
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.

12.  DIGITALIS
 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
 commercially produced in Holland, Equador, USA
DIGITALIS PURPUREA – PURPLE FOXGLOVE
 Digitalis consists of the dried leaves of Digitalis purpurea.
 It is required to contain at least 0.3% of total cardienolides calculated as
digitoxin.

13.  Glycosides
 purpurea glycoside A
 purpurea glycoside B
 Glucogitaloxin
 Steroid cardenolides
 contains 30 glycosides, 6 main ones
 only has 3 aglycones
 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

14. Digitalis lanata contains cardiac glycosides like lanatoside A, B, C and E.
Lanatosides A and B are acetyl derivatives of purpurea glycosides A and B
respectively.
Hydrolysis of Lanatoside C yields digoxin, a crystalline active glycoside.
Biochemical Mechanism of Action
The mechanism whereby cardiac glycosides cause a positive inotropic effect.
Several mechanisms have been proposed.
but the most widely accepted involves the ability of cardiac glycosides to
inhibit the membrane bound Na+-K+-ATPase pump responsible for Na+-K+
exchange.
The process of membrane depolarization / repolarization is controlled by the
movement of three cations, Na+, Ca+2, and K+, in and out of the cell.

16.  Medicinal Uses
 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.
 it stimulates the flow of urine which lowers the volume of the
blood and lessens the load on the heart