CARDIAC

GLYCOSIDES

Presented by
Mr. R. A. Ahirrao
Assistant Professor
College of Pharmacy,
Shahada 1
CARDIAC GLYCOSIDES OR
STEROLS
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.

Lactone ring
12 CH3
17
Cyclopentano per 11 13
hudro phenanthrene 1 16
R 9 14
2 15
10 8 OH
3
7
Sugar O 5
4 6
 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.
General properties of Cardiac Glycosides :
Amorphous powder
Bitter taste
Solubility in H2O
Insolubility in Organic solvents
Very toxic compounds
Odorless
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
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.
 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 A
 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
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.
These sugars predominantly exist in the cardiac
glycosides in the β-conformation.

Digitose
Digitoxose
CHEMICAL IDENTIFICATION:
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)
 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.
 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
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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Morphology of thevetia seed:
Color: green to greyish black
Odour: none
Taste: Bitter & produce numbness when chewed
Shape : oblong
Size ; upto 7 cm