Glycosides Lecture PDF

9/29/2024 Glycosides Bader S. Alabdullah Glycosides Glycosides are organic compounds that, upon hydrolysis, yield one or more sugars (glycone) and a non-sugar component (aglycone or genin) The most common sugar found in glycosides is D-glucose...

9/29/2024 Glycosides Bader S. Alabdullah Glycosides Glycosides are organic compounds that, upon hydrolysis, yield one or more sugars (glycone) and a non-sugar component (aglycone or genin) The most common sugar found in glycosides is D-glucose Many glycosides also contain other sugars like rhamnose, digitoxose, and cymarose Glycosides are widespread in plants and play crucial roles in plant metabolism, defense, and regulation 9/29/2024 Bader S. Aladullah 2 1  9/29/2024 Glycosides (cont.) In chemical terms, glycosides are acetals, where the hydroxyl group of the sugar is condensed with the hydroxyl group of the aglycone Structurally, glycosides can be classified into alpha and beta glycosides, based on the configuration of the glycosidic linkage In plants, only the beta glycosides are commonly found, and specific enzymes like emulsin are responsible for their hydrolysis 9/29/2024 Bader S. Aladullah 3 Biological Importance of Glycosides Glycosides act as defense mechanisms, regulators, and storage forms of bioactive compounds Some plants use glycosides to store toxic aglycones that can be released when the plant is damaged 9/29/2024 Bader S. Aladullah 4 2  9/29/2024 Therapeutic and Medicinal Uses of Glycosides Glycosides are also of paramount importance in pharmacognosy and medicine Cardiac glycosides: These glycosides, found in plants like digitalis, are used to treat heart failure and cardiac arrhythmias. Laxative glycosides: Found in plants such as senna and aloe, these glycosides help stimulate bowel movements. Cyanogenic glycosides: These compounds release hydrocyanic acid upon hydrolysis and have toxic as well as potential medicinal properties, though their use in medicine remains controversial 9/29/2024 Bader S. Aladullah 5 Classification of Glycosides Glycosides can be classified based on several criteria: 1. By Sugar Group: D-glucose, digitoxose, rhamnose, and cymarose 2. By Aglycone Group: Tannins, steroids, flavonoids, and terpenoids 3. By Therapeutic Action: To treat heart disease, used as laxatives, and used for their surfactant effects 9/29/2024 Bader S. Aladullah 6 3  9/29/2024 Glycoside Biosynthesis The biosynthesis of glycosides involves a glycosyl transferase reaction This reaction occurs in a two-step process: 9/29/2024 Bader S. Aladullah 7 Glycoside Biosynthesis (cont.) 1. Formation of UDP-Sugar: The sugar phosphate (such as glucose-1-phosphate) reacts with uridine triphosphate (UTP), forming uridine diphosphate-glucose (UDP-glucose) This reaction is catalyzed by uridyl transferase UTP + Sugar-1-P UDP-Sugar + PPi 9/29/2024 Bader S. Aladullah 8 4  9/29/2024 Glycoside Biosynthesis (cont.) 2. Transfer of Sugar to Aglycone: The enzyme glycosyl transferase catalyzes the transfer of the sugar from UDP-sugar to the aglycone, forming the glycoside UDP-Sugar + Aglycone Glycoside + UDP 9/29/2024 Bader S. Aladullah 9 Glycoside Biosynthesis (cont.) Example is the biosynthesis of prunasin, a cyanogenic glycoside In this process, phenylalanine undergoes several transformations to form intermediates like nitriles and cyanohydrins, ultimately yielding prunasin This pathway is highly stereospecific, meaning that enzymes in different plant species produce different stereoisomers of the final glycoside product 9/29/2024 Bader S. Aladullah 10 5  9/29/2024 Glycoside Biosynthesis (cont.) 9/29/2024 Bader S. Aladullah 11 Types of Glycosides (cont.) 1. Cardiac Glycosides: One of the most therapeutically valuable types of glycosides Extracted from plants such as Digitalis purpurea (foxglove), Strophanthus, and Convallaria (lily of the valley) Used to manage heart failure and certain arrhythmias Increasing the force of heart contractions Slowing the heart rate Inhibiting the Na+/K+-ATPase 9/29/2024 Bader S. Aladullah 12 6  9/29/2024 Types of Glycosides (cont.) 1. Cardiac Glycosides: Digoxin: A cardiac glycoside used in the treatment of heart conditions It is isolated from Digitalis species Ouabain: Derived from Strophanthus gratus It is a potent inhibitor of the Na+/K+-ATPase pump Has a similar mechanism of action to digoxin Cardiac glycosides have narrow therapeutic window Require careful monitoring to avoid toxic side effects Arrhythmias and gastrointestinal disturbances. 9/29/2024 Bader S. Aladullah 13 Types of Glycosides (cont.) 9/29/2024 Bader S. Aladullah 14 7  9/29/2024 Types of Glycosides (cont.) 2. Anthraquinone Glycosides: They are well known for their laxative effects They are found in plants like aloe, senna, and cascara sagrada They act by stimulating the contraction of the smooth muscle in the large intestine Promoting bowel movements 9/29/2024 Bader S. Aladullah 15 Types of Glycosides (cont.) 2. Anthraquinone Glycosides: Cascara Sagrada: Derived from the bark of Rhamnus purshiana It contains both O-glycosides (such as emodin) and C-glycosides (such as barbaloin) The primary use is as a laxative, particularly in cases of chronic constipation Fresh bark contains reduced forms of glycosides, which are transformed into more potent forms during storage This aging process ensures that the glycosides exhibit their desired laxative effects with reduced irritation to the intestinal mucosa 9/29/2024 Bader S. Aladullah 16 8  9/29/2024 Types of Glycosides (cont.) 9/29/2024 Bader S. Aladullah 17 Types of Glycosides (cont.) 2. Anthraquinone Glycosides: Senna: The glycosides in senna, known as sennosides, are responsible for the plant's potent laxative action Sennosides A and B are dimeric glycosides containing rhein and aloe- emodin as aglycones These compounds work by increasing the peristaltic action of the colon Senna is widely used in over-the-counter laxative preparations 9/29/2024 Bader S. Aladullah 18 9  9/29/2024 Types of Glycosides (cont.) 9/29/2024 Bader S. Aladullah 19 Types of Glycosides (cont.) 3. Saponin Glycosides Saponins are glycosides that form colloidal solutions and foam when shaken These glycosides are known for their hemolytic activity and toxicity Saponins are found in a variety of plants, including Glycyrrhiza glabra (licorice), Dioscorea (yam), and Sarsaparilla They have a wide range of applications, from medicinal uses as expectorants and diuretics to industrial uses as surfactants 9/29/2024 Bader S. Aladullah 20 10  9/29/2024 Types of Glycosides (cont.) 3. Saponin Glycosides: Glycyrrhiza (Licorice): Licorice root contains the saponin glycoside glycyrrhizin, which is 50 times sweeter than sucrose Glycyrrhizin has been used in traditional medicine to treat ulcers, respiratory conditions, and as an anti-inflammatory agent In modern pharmacology, glycyrrhetic acid, the aglycone of glycyrrhizin, has been studied for its potential to treat gastric ulcers and adrenal insufficiency Licorice is also widely used as a flavoring agent in candy and tobacco products 9/29/2024 Bader S. Aladullah 21 Types of Glycosides (cont.) 9/29/2024 Bader S. Aladullah 22 11  9/29/2024 Types of Glycosides (cont.) 3. Saponin Glycosides: Saponins in Cortisone Production: Plants such as Dioscorea (Mexican yam) and Agave are rich in steroidal sapogenins, such as diosgenin and hecogenin These compounds serve as precursors for the synthesis of cortisone The steroid nucleus in these sapogenins makes them valuable for pharmaceutical manufacturing 9/29/2024 Bader S. Aladullah 23 Types of Glycosides (cont.) 9/29/2024 Bader S. Aladullah 24 12  9/29/2024 Types of Glycosides (cont.) 4. Cyanogenic Glycosides: Amygdalin and Laetrile: Amygdalin has been the subject of significant research due to its potential anti-cancer properties Laetrile, a semi-synthetic derivative of amygdalin, has been promoted as a cancer treatment, although its efficacy remains controversial The release of hydrocyanic acid is thought to be responsible for its purported anti-cancer effects The FDA has not recognized laetrile as an effective cancer treatment 9/29/2024 Bader S. Aladullah 25 Types of Glycosides (cont.) 9/29/2024 Bader S. Aladullah 26 13  9/29/2024 Types of Glycosides (cont.) 4. Cyanogenic Glycosides: Prunasin: Found in Prunus serotina (wild cherry) Prunasin is another cyanogenic glycoside that releases mandelonitrile, which decomposes to form benzaldehyde and HCN Wild cherry bark is used in traditional medicine as an expectorant and cough suppressant, particularly in the form of syrups 9/29/2024 Bader S. Aladullah 27 Types of Glycosides (cont.) 5. Flavonol Glycosides: Flavonol glycosides are a group of compounds with flavonoid aglycones Flavonoids are polyphenolic compounds known for their antioxidant properties Protect cells from oxidative damage caused by free radicals They are also known for their potential to strengthen blood vessels and reduce capillary fragility Some well-known flavonoid glycosides include rutin, quercitrin, and hesperidin 9/29/2024 Bader S. Aladullah 28 14  9/29/2024 Types of Glycosides (cont.) 5. Flavonol Glycosides: Rutin: This flavonoid glycoside is believed to have vasoprotective properties Helping to strengthen blood vessels and reduce capillary permeability Rutin is often used in the treatment of conditions characterized by capillary fragility, such as hemorrhoids and varicose veins 9/29/2024 Bader S. Aladullah 29 Types of Glycosides (cont.) 9/29/2024 Bader S. Aladullah 30 15  9/29/2024 Types of Glycosides (cont.) 5. Flavonol Glycosides: Hesperidin: Found in citrus fruits Hesperidin has been studied for its potential anti-inflammatory and antioxidant effects It is often included in supplements aimed at promoting cardiovascular health 9/29/2024 Bader S. Aladullah 31 Types of Glycosides (cont.) 9/29/2024 Bader S. Aladullah 32 16  9/29/2024 Types of Glycosides (cont.) 6. Phenol Glycosides: Phenol glycosides contain phenolic aglycones Known for their anti-inflammatory and analgesic properties A well-known example is salicin Found in willow bark and poplar bark Salicin is converted to salicylic acid in the body Which has analgesic, antipyretic, and anti-inflammatory effects Salicin was historically used in the development of aspirin 9/29/2024 Bader S. Aladullah 33 Types of Glycosides (cont.) 9/29/2024 Bader S. Aladullah 34 17  9/29/2024 Types of Glycosides (cont.) 6. Phenol Glycosides: Arbutin: Found in uva ursi and chimaphila Arbutin is a phenol glycoside that yields hydroquinone upon hydrolysis Arbutin has been used traditionally for its diuretic and urinary antiseptic properties Particularly in the treatment of urinary tract infections 9/29/2024 Bader S. Aladullah 35 Types of Glycosides (cont.) 9/29/2024 Bader S. Aladullah 36 18  9/29/2024 Tannins Tannins are complex polyphenolic compounds found widely in the plant kingdom They have been used for centuries in medicine due to their astringent properties Which allow them to precipitate proteins and form protective barriers on mucous membranes Tannins are divided into two major classes: 9/29/2024 Bader S. Aladullah 37 Tannins 1. Hydrolyzable Tannins: These tannins are made up of gallic acid or related polyhydric compounds esterified with sugars, usually glucose Upon hydrolysis, they yield the phenolic acids and sugars Hydrolyzable tannins are commonly found in plants like oak and chestnut 9/29/2024 Bader S. Aladullah 38 19  9/29/2024 Tannins 9/29/2024 Bader S. Aladullah 39 Tannins 9/29/2024 Bader S. Aladullah 40 20  9/29/2024 Tannins (cont.) 2. Condensed Tannins: These tannins are composed of flavan-3-ols or flavan-3,4-diols Condensed tannins do not hydrolyze easily and tend to form phlobaphenes Which are insoluble red-colored compounds These tannins are often found in plants like grape and tea 9/29/2024 Bader S. Aladullah 41 Tannins (cont.) 9/29/2024 Bader S. Aladullah 42 21  9/29/2024 Tannins (cont.) Tannins are non-crystallizable compounds that form colloidal solutions in water Their ability to bind with proteins and precipitate them from solution makes them useful in treating conditions like diarrhea and inflammation Tannins are also used externally as astringents to treat wounds and prevent infection 9/29/2024 Bader S. Aladullah 43 9/29/2024 Bader S. Aladullah 44 22