This document summarizes the biological evaluation of plant-derived drug molecules digoxin and digitoxin. It discusses that biological evaluation is used when drugs cannot be fully evaluated by chemical and physical methods alone. The response of a test drug is compared to a standard preparation using living systems, and activity is measured in International Units. Digoxin and digitoxin are cardiac glycosides obtained from Digitalis plants that act as cardio-tonic agents, increasing heart muscle tone, excitability and contractility. Their isolation, biosynthesis, structure-activity relationships, and uses are described.

1. Presentation:
PHYTOCHEMISTRY
Submitted To: Submitted By:
Dr. Malik Saadullah M. Rashad (616)
M. Shan (621)

2. BIOLOGICAL EVALUATION OF
PLANT DERIVED DRUG
MOLECULES
(DIGOXIN & DIGITOXIN)

3. • Introduction:
(1) Drug evaluation may be defined as the
determination of identity, purity and quality
of a drug.
(2) Identity – identification of biological source
of the drug.
(3) Quality – the quantity of the active
constituents present.
(4) Purity – the extent of foreign organic material
present in a crude drug.

4. Biological Evaluation:
• It is employed when the drug cannot be
evaluated satisfactorily by chemical and
physical methods.
• In this method, the response produced by the
test drug on a living system is compared with
that of the stranded preparation.
• Such an activity is represented in units as
International Units (I.U).

5. Indication of Biological Evaluation:
• When the chemical nature of the drug is not
known but is has an biological action.
• When chemical methods are not available.
• When the quantity of the drug is small and so
it cannot be evaluated chemically.
• Drugs which have different chemical
composition but same biological activity.
• Example: Cardiac glycosides arte evaluated by
this method on cats, frogs or pigeons.

6. Cardiac Glycosides:
•The genins of all cardiac glycosides are steroidal in
nature, that act as cardio tonic 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.
•There are two main constituents of Digitalis plant.
1. Digoxin is obtained from Digitalis lanata.
2. Digitoxin is obtained from Digitalis purpurae.
Compounds R1 R2
Digitoxigenin H H
Digoxigenin OH H

7. ISOLATION Digitalis powder
Removal of fatty material by extraction with petroleum ether
Digestion of defatted material with water
Liquid discard Extracted more with several water and ethanol mixture
Concentrate to small volume
Distillation in vaccum
Precipitation of tannin by lead hydroxide
Super gel filtration
Glycoside with low
Solubility in water &
High solubility in
chloroform
Glycoside with low
Solubility in water &
High solubility in
chloroform

8. Aqueous solution
Extraction with
chloroform
Washing with chloroform with water
2N HCl, 2N Na2CO3.
Discard washing
Separation of glycoside by
chromatography
Elution with chloroform
& chloroform containing graded
proportion of methanol
Adjust filtrate to pH 6
Successive washing with chloroform
Ether. ethanol
Discard washing
Into aqueous phase add
Sodium sulfate to saturation
Extraction with chloroform ethanol mixture
Acetylation/ benzoylation
of more polar glycoside
KHCO3
Separation of individual glycoside
By chromatography
Less polar
glycoside

9. Biosynthesis of Digoxigenin & Digitoxigenin

10. SAR
1. The glycone part displays a great influence on the
solubility and the rate of
absorption and distribution of the glycosides to the
site of action.
2. Small change in the molecules such as a change of
the location of the OH group, modify the cardiac
activity or even eliminate it completely.
3. The saturation and/or cleavage of the lactone ring,
destroys the cardiac activity. Therefore, the closely
related CG, differ greatly in the rate of absorption,
duration of action and their cumulative effect.

11. USES:
• Heart failure with sinus rhythm or atrial fibrilation.
• Atrial flutter.
• Paroxysmal atrial tachcardia.
• Prevention of paroxysmal atrial arrythmias.
• Prophylactically before cardiac surgery.