Steroidal Nucleus Structure and Activity Relationship

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Questions and Answers

What is the effect of higher number of -OH groups on the steroidal nucleus?

Rapid onset of action and faster elimination from the body (correct)

Slower onset of action and longer elimination from the body

Increased potency but slower elimination from the body

No effect on the onset of action and elimination from the body

What is the result of replacing -OH groups at C3 and/or C14 by H atoms?

No effect on potency

Significant reduction of potency

Slight reduction of potency (correct)

Increased potency

What is the orientation of the C17 side chain required for activity?

No specific orientation is required

β-orientation (correct)

α-orientation

γ-orientation

What is the effect of the sugar moiety on cardiac glycosides?

It has no cardiac activity Signup and view all the answers

Which of the following is more potent?

Cardiac glycosides with 6-CH3 sugars Signup and view all the answers

What is the trend in potency with increasing number of sugar units in oligosaccharide moieties?

Potency decreases with increasing number of sugar units Signup and view all the answers

Which plant is a source of cardiac glycosides?

Both A and B Signup and view all the answers

What is the commercial source of Digitalis lanata?

Ecuador, USA, and Holland Signup and view all the answers

What is the principal glycoside of the wood of the African Acokanthera schimperi?

Ouabain Signup and view all the answers

What is the cardiac effect of Thevetia peruviana glycosides?

Myocardial insufficiency and digitalis intolerance Signup and view all the answers

What is the result of partial hydrolysis of Thevetia peruviana glycosides?

Formation of Peruvoside Signup and view all the answers

What is the family of plants that Calotropis spp belongs to?

Asclepiadaceae Signup and view all the answers

What is the use of Bufadienolides as cardioactive drugs?

Therapeutically little used due to their low therapeutic index Signup and view all the answers

What is the reagent used in Legal's test for cardiac glycosides?

Na nitroprusside + NaOH Signup and view all the answers

What is the result of Keller-Killiani's test for cardiac glycosides?

A blue ring between the two layers Signup and view all the answers

What is the name of the glycoside isolated from Urginea maritima?

Scillaren A Signup and view all the answers

Study Notes

Oxygen Substitution on Steroidal Nucleus

Higher number of -OH groups results in more rapid onset of action and elimination from the body.
Replacement of -OH groups at C3 and/or C14 by H atoms results in slight reduction of potency.

Structure Activity Relationship

β-orientation of C17 side chain is necessary for activity, 17α-cardenolides (allocardenolides) are inactive.
Sugar moiety has no cardiac activity, but when attached to C3 -OH group of steroidal moiety, activity is modified and influences pharmacokinetic behavior.
Free aglycones are less potent than their glycosides.
Type and number of sugar units may affect potency.
Cardiac glycosides with 6-deoxy sugars (6-CH3) are more potent than their 6-CH2OH analogs.
For oligosaccharide moieties, potency decreases with increase in number of sugar units.

Distribution in Nature

Scrophulariaceae (Digitalis purpurea leaves - foxglove, Digitalis lanata leaves - white flowers)
Apocyanaceae (Strophanthus kombe vine seeds - Africa)
Liliceae (Urginea bulbs - squill, Europe, India)
In toads (cardiac glycosides are also found in animals only in exceptional cases)

Digitalis

Digitalis spp (Scrophulariaceae)
D. lanata: Mediterranean/White, commercially produced in Ecuador, USA, and Holland (total glycosides, 1.5%) with major: Lanatosides A-E (primary glycosides) and digoxin.
D. purpurea: British/Purple, commercially produced in Holland and Eastern Europe (total 0.5%) with major: Purpurea glycosides A, B, and E, digitoxin, gitoxin, and gitaloxin.

Strophanthidin

Seeds of East African Strophanthus kombé were formerly official in the BP.
Principal glycosides: K-strophanthoside, K-strophanthin, and cymarin, all based on the genin strophanthidin.
Also found in Strophanthus hispidus.

Ouabain

The principal glycoside of the wood of the African Acokanthera schimperi (A. ouabaio).
Strophanthus gratus seeds contain 4-8% of ouabain (G-strophanthin), a rhamnose glycoside more stable than those present in other species.

Oleander Glycosides

Thevetia peruviana (T. neriifolia) - yellow oleander, are a rich source of the glycoside thevetin A.
Partial hydrolysis and the loss of two glucose units yields peruvoside.
Peruvoside consists of L-thevetose linked to the aglycone cannogenin.

Other Sources

Calotropis spp
Asclepiadaceae
Convallaria majalis (Liliaceae) - Lily of the Valley

Bufadienolides

Found in some Liliaceae and Ranunculaceae, and in the toad venoms.
The genins are partly free and partly combined with suberyl arginine.
Therapeutically, they find little use as cardioactive drugs because of their low therapeutic index and their production of side effects.

Urginea maritima

Squill
Scillaren A, and an amorphous mixture of glycosides, scillaren B isolated.
Scillaren A is the most important cardiac glycoside.

Chemical Testing

Colour tests based on the aglycone:
- Legal's test: deep red color.
- Raymond's test: violet color - blue color.
- Kedde's test: violet color.
- Baljet's test: orange or red.
Liebermann's test and Antimony test will give a positive reaction.
Colour tests based on the glycone:
- Keller-Killiani's test (for 2-deoxy sugar): a blue ring between the 2 layers is a positive reaction.

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Description

This quiz covers the effects of oxygen substitution on the steroidal nucleus on distribution, metabolism, and potency, as well as the importance of β-orientation of the C17 side chain and sugar moiety on cardiac activity. Learn how structural changes impact the activity of steroids.