Glycosides

• <S>:Cardiac glycosides are a class of organic compounds found in certain plants (particularly the rosemary and foxglove families) that can be effective drugs in treating abnormal heart rhythms or heart failure.
• Glycosides are compounds that yield one or more sugars among the products of hydrolysis
• Glycosides are involved in the regulatory, protective, and sanitary functions of plants
• Glycosides are classified based on the chemical nature of the aglycone
• Glucoside refers to the substance where the sugar formed is glucose
• In glycosides, α and β varieties exist, but only the β variety occurs in plants
• Emulsin and myrosin are enzymes that can hydrolyze more than one glycoside
• Components of glycosides:

  • Sugar (glycone) – sugar component
  • Non-sugar (aglycone) – non-sugar component
• Glycosides play an important role in the life of the plant and are involved in its regulatory, protective, and sanitary functions
• Glycosides have therapeutically active agents valuable to humans, such as cardiac drugs and laxatives
• Examples of Glycosides:

  • Cardiac Glycosides: Digitalis, Strophanthus, Squill, Convallaria, Apocynum
  • Laxatives Glycosides: Senna, Aloe, Rhubarb, Cascara sagrada, Frangula, Black Mustard, White Mustard, Wintergreen
• Biosynthesis of Glycosides involves the transfer of a uridylyl group from uridine triphosphate to a sugar 1-phosphate (glycone) by an enzyme known as uridylyl transferase
• Biosynthesis of Glycosides also involves the transfer of the subsequent reaction of sugar by the mediation of glycosyl transferase from uridine diphosphate to a suitable acceptor (aglycone) forming the glycoside
• Classification of Glycoside Containing Drugs:

  1. Anthraquinone Glycosides

  2. Cardioactive Glycosides

  3. Saponin Glycosides

  4. Cyanophore Glycosides

  5. Isothiocyanate Glycosides

  6. Flavonol Glycosides

  7. Alcohol Glycosides

  8. Aldehyde Glycosides

  9. Lactone Glycosides

  10. Phenol Glycosides
• Anthraquinone Glycosides:

  • Are glycosides with aglycones related to anthracene
  • Yields upon hydrolysis aglycones that are di-, tri-, or tetra-hydroxyanthraquinones or modifications of these compounds
  • Examples include Frangulin (emodin + rhamnose) with uses as a stimulant cathartic/laxative
• Biosynthesis of Anthraquinone Glycosides:

  • Obtained from studies of microorganisms like Penicillium islandicum
  • Anthranols and anthrones are intermediates in the formation of anthraquinones
• Cardiac glycosides usually contain 3 to 4 sugars attached at C-3 OH, including glucose, rhamnose, and deoxysugars
• Glycosides are soluble in water and alcohols
• The number of sugars in glycosides affects their water solubility
• Aglycones in glycosides are soluble in CHCl3 and EtOAc
• Stability of cardiac glycosides:

  • Acid hydrolysis splits sugars from the aglycone first
  • Enzymatic hydrolysis splits sugars stepwise starting from the terminal sugar
  • Elevated temperature causes dehydration by removing the C-14 OH group to give an inactive anhydro-form
• Cardiac glycosides are used as cardiotonics to treat congestive heart failure
• Cardiac glycosides increase the force of contraction of cardiac muscles without increasing oxygen consumption
• Cardiac glycosides increase cardiac output and prolong the diastolic phase, decreasing heart rate
• Cardiac glycosides have a diuretic effect due to their direct action on renal tubules, increasing the amount of blood passing through the kidney
• Plants containing cardiac glycosides:

  • Digitalis (Foxglove) from Digitalis purpurea and Digitalis lanata
  • Strophanthus from Strophanthus kombé
  • Squill (Urginea maritima)
• Squill, also known as Scilla or Maritime squill, is derived from the sliced, dried, fleshy middle scales of the onion of the white variety of Urginea maritima
• Squill's principal active constituent is Bufadienolides, which are aglycones containing only two hydroxyl groups at C-3 and C-14, and it has a 6-membered lactone ring
• Squill is used for its medicinal properties, including increasing cardiac contractility, controlling heart rate and atrial fibrillation, and as an antiarrhythmic agent
• Squill is also known for its historical use as a source of arrow poison
• Araliaceae is known as the Ginseng family
• Protopanaxdiols and b-Protopanaxatriols are classifications related to Araliaceae
• Ginseng has an adaptogenic effect, improving physical and mental performance, immune function, metabolism, liver functions, and stabilizing blood glucose and pressure
• Horse Chestnut is derived from Aesculus hippocastanum and is used for anti-inflammatory purposes and peripheral vascular disorders like varicose veins and hemorrhoids
• Glycyrrhiza, known as Licorice root, has active constituent Glycyrrhizin, used for various purposes like demulcent, expectorant, flavorant, and anti-inflammatory properties
• Senega is derived from Polygala senega and is used as a stimulant expectorant in chronic bronchitis
• Cyanophore glycosides refer to glycosides found in rosaceous plants that yield hydrocyanic acid upon hydrolysis
• Wild Cherry, derived from Prunus serotina, is used as a flavored vehicle in cough remedies and as a sedative expectorant
• Isothiocyanate glycosides come from cruciferous plants and contain aglycones that are isothiocyanates, used as local irritants, emetics, rubefacients, vesicants, and condiments
• Flavonol glycosides, known as flavonoids, are plant pigments synthesized from phenylalanine, classified into flavones, flavonols, and flavonones