The Cardiac Glycosides Cardio-active Glycosides A Group of steroidal glycosides act as cardiotonic agent. They increase tone, excitability and contractility of cardiac muscles.

Structural features: -Steroidal nucleus must be present. -3  -OH group involved in glycosidic linkage. -14  -OH group at C 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. -The presence of lactone ring: 14

According to the type of lactone ring Cardiac Glycosides are classified into: –Cardinolides: They are C-23 containing 5-membered unsaturated lactone ring e.g. Digitalis & Strophanthus –Bufadienolides: They are C-24 containing 6-membered unsaturated lactone ring e.g. Squill

The Sugar Part: The glycosides usually contain 3 to 4 sugars attached at C-3 OH. Beside Glucose and Rhamnose they usually contain deoxysugars.

The Cardinolides 1- Digitalis Glycosides Digitalis is Known as “foxglove” The most important species includes: 1) Digitalis purpurea 2) Digitalis lanata

Digitalis contain three major aglycones:

2- Strophanthus Glycosides Obtained from Strophanthus komb é The used part is the seeds. The common aglycone is K-strophanthidin

10 14

Bufadienolides 1- Squill Glycosides They have 6-membered lactone ring. Obtained from Squill bulbs. Aglycone contains only two hydroxyl groups at C-3 and C-14.

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 CHCl 3 and EtOAc.

Stability: –1) Acid hydrolysis: Split sugars from the aglycone first. –2) Enzymatic hydrolysis: Split sugars stepwise starting from the terminal sugar. –3) Elevated temperature: Cause dehydration by removal of C-14 OH group to give inactive anhydro-form

Medicinal Importance: -They are Cardiotonics used to treat Congestive heart failure. -They increase force of contraction of cardiac muscles without increasing oxygen consumption. -Increase cardiac output. The diastolic phase lasts longer, thus decreases heart rate. -Have diuretic effect due to increase amount of blood passing through the kidney.

Chemical Identification: General test for steroids: Liebermann’s test: Glycoside in acetic anhydride + Few drops of conc. H 2 SO 4 Reddish violet Green Test for Deoxysugars: Keller-Kiliani’s Test: Glycoside in gl. acetic containing traces of FeCl 3 + conc. H 2 SO 4 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: –Legal’s test: Cardenolide in pyridine + Na nitroprusside + NaOH  deep red colour. –Kedde’s test : Cardenolide + 3,5 dinitrobenzoic acid (Kedde’s reagent A) + NaOH (Kedde’s reagent B)  violet colour.