Sterol or Cardiac Glycosides

STEROL OR CARDIAC GLYCOSIDES

The cardiac glycosides are an important class of naturally occurring drugs whose actions include both beneficial and toxic effects on the heart. Plants containing cardiac steroids have been used as poisons and heart drugs at least since 1500 B.C. Throughout history these plants or their extracts have been variously used as arrow poisons, emetics, diuretics and heart tonics. Cardiac steroids are widely used in the modern treatment of congestive heart failure and for treatment of atrial fibrillation and flutter. Yet their toxicity remains a serious problem. These drugs all act by affecting the availability of intracellular Ca⁺² for myocardial contraction or increasing the sensitivity of myocardial contractile proteins.

Cardiac glycosides are composed of two structural fea-tures: the sugar (glycone) and the nonsugar (aglycone– steroid) moieties.

The steroid nucleus has a unique set of fused ring system that makes the aglycone moiety structurally distinct from the other more common steroid ring systems. The steroid nucleus has hydroxyls at 3- and 14-positions of which the sugar attachment uses the 3-OH group. 14-OH is normally unsubstituted. Many genins have OH groups at 12- and 16-positions. These additional hydroxyl groups influence the partitioning of the cardiac glycosides into the aqueous media and greatly affect the duration of action. The lactone moiety at C-17 position is an important structural feature. The size and degree of unsaturation varies with the source of the glycoside. Normally plant sources provide a five-membered unsaturated lactone while animal sources give a six-membered unsaturated lactone.

One to four sugars are found to be present in most cardiac glycosides attached to the 3β-OH group. The sugars most commonly used include L-rhamnose, D-glucose, D-digitoxose, D-digitalose, D-digginose, D-sarmentose, L-vallarose and D-fructose. These sugars predominantly exist in the cardiac glycosides in the β-conformation. The presence of acetyl group on the sugar affects the lipophilic character and the kinetics of the entire glycoside.

Two classes have been observed in nature—the cardenolides and the bufadienolides.

The cardenolides have an unsaturated butyrolactone ring while the bufadienolides have a pyrone ring. The lactone of cardenolides has a single double bond and is attached at the C-17 position of steroidal nucleus. They are five-membered lactone ring and form a C₂₃ steroids (Leguminosae, Cruciferae, Euphorbiaceae, etc.), while the lactone of bufadienolids have two double bond which is attached at the 17 α-position of the steroidal nucleus. They are six-memberd lactone ring and form C₂₄ steroids (Liliaceae, Ranunculaceae).