DEGOXIN

1. PHYTOCHEMISTRY OF
DIGOXINE AND LANATOSIDES
Presented by
G.Srikavya
M.Pharmacy
Pharmcognosy And Phytochemistry
H.No: 22004P1014
University College of Pharmaceutical Sciences 1

2.  Source of Digoxin.
 Chemical Structure.
 Structural Features.
 Chemical constituents
 Mechanism of Action.
 Structural activity relationship.
 Chemical tests.
 Therapeutic Uses of Digoxin.

3. 1.DIGOXIN :
Digoxin flowers
3

4. Sources Of Digoxin:
 Synonym : Woolly fox glove leaf, Austrial digitalis.
 Biological source :These are the dried leaves of Digitalis
Lanata Ehrhart.
 Family : Scrophulariaceae.
 Geographical source : It is cultivated and collected in
England, other parts of Europe, united states and India.
4

5. Chemical Structure:
Iupac name: (3, 5, 12beta)-3((O-2,6-dideoxy-beta-D-
ribohexanosyl –(1 4) O-2,6 dideoxy beta D ribohexopyranosyl
(1 4)2,6 dideoxy beta D-ribohexanopyranosyl) oxy)-
12,14dihydroxy card-20(22) enolide).
5
A
B
C
D
A B
C D

6.  Steroidal nucleus is
present.
 3β-OH group involved
in glycosidic linkage.
 14β-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
R
OH
sug-O
R2
R1
3
5
12
16
17
R3
H
H
H
B
A
C
D

7. According to the type of lactone ring
Cardiac glycosides are classified into:
• CARDINOLIDES:
They are C-23 containing 5membered
unsaturated lactone ring
eg: digitalis and strophanthus
• BUFADIENOLIDES:
• They are C-24 conatininng
6membered unsaturated latone ring
• Eg:squill
O
O
17
17
O
O

8. Chemical Constituents:
 It contains 5-primary glycosides and in all about 70
Cardiac glycosides.
 The primary glycosides are identified as Lanatocides
A,B,C,D and E.
It should be noted that glycone Digitaxose and not
aglycone is acetylated.
The inter relationship of Cardiac glycosides and their
glycones of Digitalis Purpurea and Digitalis Lanata.
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9. Mechanism Of Action:
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10. Drug Interactions And Mechanism:

S.NO Interacting drug Effect of Digoxin Mechanism
1 Quinidine 2-3 times increase in
Plasma level
Reduced renal or
renal clearence
2 Verapamil Decrease Pulse rate Reduced
clearence
3 Adrenergic drugs Tachy- Arrhythmias Increase
myocardial
sensitivity
4 Propanolol More Bradycardia
,Dicrease Inotropic ction
Additive AV
nodal depression
5 Anti bacterials Increase Bioavailability Reduced Gut
interaction
10

11. Structural Activity Relationship(SAR):
11
A
B
D
C
C
A B
C D

12. 1. The cardiac activity is linked to the aglycone.
2. The sugar moiety does not participate directly in the
activity, but its presence enhances the activity and
modulates it by modifying the polarity of the compound.
3.The lactone at C17, the presence of X=C-C= function (
were x is heteroatom ) is required, it must be in the β-
configuration .
12

13. • The C and D rings must be cis fused.
• The substituent's, the inversion of the configuration at
C-3 diminishes the activity, but -3-deoxy compounds
are not completely inactive.
• The 3o alcohol function at C-14 .
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14. 6. 14-Epidigitoxigenin is inactive where as 14-
deoxydigitoxigenin ( with a 14 β –hydrogen ) is slightly
active (although 8β, 14β epoxy derivatives are inactive).
7. None of the countless modification attempted in this
series has improved the performance of the natural
glycosides.
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15. Chemical Test:
 Keller –Killani test for Digitoxose:
The test consists of boiling about 1g finely powdered
digitalis with 10ml70 % alcohol for 2-3minutes.
 The extract is filtered to the filtrate is added 5ml H2O and
0.5 ml strong solution of Pb-acetate.
The filtrate is treated with equal volume of CHCl3 and
evoparated to yield the extractive.
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16.  The extractive is dissolved in glacial acetic acid and after
cooling 2 drops Fecl3 solution is added to it.
 These contents are transferred to a test tube containing
2ml concentrated H2SO4.
 A reddish brown layer acquiring bluish green colour after
standing is absorved due to the presence of Digitoxose.
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17. Legals Test:
The extract is dissolved in Pyridine, Sodium nitro prusside
solution is added to it and made alkaline
Pink or Red colour is produced.
Baljet test:
 To a selection of digitalis, Sodium picrate solution is
added it shows Yellow-Orange colour.
 Foreign organic matter : NMT 2%.
 Acid insoluble ash : NMT 5%.
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18. Therapeutic Uses Of Digoxin:
 The therapeutic uses of digoxin are given below.
1. Chronic CHF with atrial Fibrillation.
2. Chronic CHF with normal sinus rhythm.
3. Chronic atrial fibrillation.
4. Paroxysmal atrial tachycardia.
5. Atrial flutter.
6. Left ventricular failure .
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19. 1. Chronic CHF with atrial fibrillation :
 Digoxin reduces heart rate by AV block and Increases out
put
2. Chronic CHF with normal Sinus rhythm :
 Digoxin provides limited clinical benefits from
congestive manifestation
 It increases cardiac output gradually even when given in
smaller dose
3. Chronic atrial fibrillation with out CHF :
 In this condition the main objective is to reduce
ventricular rate by Digoxin
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20. 4. Paroxysmal atrial Tachycardia :
 Digoxin is an alterative agent only
 The main drugs used are adenosine, Verapamil or
Diltiazem
5. Atrial fluter :
 Digoxin is less often used in this condition
6. Left ventricular failure :
 In past intravenous injection of Lanatoside –C was used in
acute CHF
It is used by i.v nitroglycerine and Frusemide.
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21. Lanatosides
Contents:
1.Biological source.
2.Structure of Lanatosides
3.Types of Lanatosides.
4. Identification tests.
5.Mechanism of action.
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22. Lanatoside:
Lanatosides flowers
22

23. Synonyms: Woolly fox glove.
Biological Source:
The digitalis consists of dried leaves of Digitalis lanata.
Family: Scrophulariaceae.
23

24. Structure Of Lanatosides:
24

25. digitoxigenin

26. Types Of Lanatoside:
Lanatoside A (Digitoxigenin).
 lanatoside B (Gitoxigenin).
 lanatoside C (Digoxigenin).
 lanatoside D (Diginatigenin).
 lanatoside E (Gitaloxigenin).
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27. Lanatosides:
Primary Glycosides in
series.
Aglycone.
1. Lanatoside A
3 β,14 β -di hydroxylated.
2.Lanatoside B 3 β ,14 β, 16β hydroxylated.
3.Lanatoside C 3 β ,14 β ,12β hydroxylated.
4. Lanatiside D 3 β , 12 β ,16 β hydroxylated [8]
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28. Identification Test:
Place of 1 mg Lanatoside-C to a small test tube having an
internal diameter of about 10mm.
Dissolve in 1ml of solution of iron chloride hexahydrate in
acetic acid and underlay gently with 1ml of H2 so4.
At the zone of content of the 2-layers a brown ring is
produced and the colour of the upper layer near the contact
zone gradually changes to blue through purple.
Finally the colour of the entire CH3COOH layer changes
to Blue-Green through deep blue.
28

29. 29
Lanatoside A Lanatoside B Lanatoside C
Alkaline hydrolysis A.H.Acetic acid A.H.Acetic acid
Acetic acid.
Purpurea glycoside A P.g. B P.g.C
Enzyme hydrolysis
Digitoxin Gitoxin Digoxin
Digitoxigenin Gitoxigenin Digoxigenin

30. Mechanism of action :
 The mechanism of Cardiac glycosides via inhibiting the
Na/K-ATP ase is in agreement with the fact that the action
of the Cardiac glycosides is enhanced by extracellular
Potassium and inhibited by high extracellular Potassium.
 The Cardiac glycosides induced changes in the
Electrophysiology of the heart also can be explained based
on the inhibition of Na/K-ATP ase .
 It has been suggested that the Intracellular loss of
Potasium because of inhibition of the Pump causes a
decrease in the cellular trancemembrane potential
approaching zero.
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31.  Once the Cardiac glycosides are absorbed, they bind
to Plasma Proteins, Digoxin has only 30% binding.
 The half-life of Digoxin in patients with normal renal
function is 1.5-2.0 days.
 Biliary excretion of digoxin is minimal .
 Digoxin is eliminated primarily unchanged by renal
tubule excreation.
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32. References:
1. C.K.Kokate, A.P.Purohit, S.B.Gokhale,
Pharmacognosy 45th edition, p.g.no: 8.10-8.23.
2. C. Veeresham, Medicinal plant biotehnology, P.g.no:
58.
3. The Merck index- 14th edition. P.g.no: 9959, 9976,
9967.
4. Edited by: Margaret F. Roberts, Michael Vink
Alkaloids biochemistry, Ecology & medicinal
applications, P.g.no: 102-122.
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33. 5. Indian pharmacopoeia, Volume 2, Ministry of Health
and Family welfare Govt. of India, New Delhi 2014
Edition.
6. A A Farooqi, B S Sreeramu, Cultivation of medicinal
and Aromatic crops.
7. David A. Williams, Thomas L-Lemke, Foye’s
principles of Medicinal Chemistry, 5th edition.
8. K. D. Tripati Essentials of Pharmacology.
33

34. 9. WWW. Drugbank. Ca
10. Wilson and Grisvolds. Organic and medicinal
chemistry, 12 th edition,
11. http:// www.drug up date .com
12. H. Wagner, S. Bladt, Plant Drug Analysis,
13. Richard A. Harvey, Pamela C. Champe,
pharmacology
14. Advances in Horti culture(Medicinal and aromatic
plants), volume 2
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