MODULE 2: CLASSES OF CHEMICAL CONSTITUENTS (I) PDF

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Summary

Glycosides - Compounds that yield one or more sugar components among the product of hydrolysis - Any molecule in which a sugar group is bonded through its anomeric carbon to another group via glycosidic bond. - A glycosidic bond is a certain type of chemical bond that joins a sugar molecule to anoth...

Description

PHARMACOGNOSY AND PLANT CHEMISTRY

Glycosides • Compounds that yield one or more sugar components among the product of hydrolysis • Any molecule in which a sugar group is bonded through its anomeric carbon to another group via glycosidic bond. • A glycosidic bond is a certain type of chemical bond that joins a sugar molecule to another molecule. • Chemically glycosides are considered as sugar- ether Components • Glycone - sugar group/sugar moiety o Glycone consist of a single sugar group (monosaccharide) or several sugar groups (oligosaccharide). o The sugars found in glycosides may be glucose and rhamnose • Aglycone or genin - nonsugar group/ nonsugar group moiety Characteristics • Solids either amorphous or crystalline • Nonvolatile • Usually bitter in taste. • Soluble in water and polar organic solvents • Reduce Fehling’s solutions only after hydrolysis. Importance of Glycosides in Plants From the biologic viewpoint, glycosides play an important role in the life of the plant. • Regulatory o Converting toxic materials to non or less toxic o Regulation of growth • Protective o Storing harmful products such as phenol o Some glycosides have antibacterial activity, so they protect the plants from bacteria and diseases. • Sanitary functions Biosynthesis • Binding of sugar to UTP • The glycosides are the condensation products of sugar and the acceptor unit called as aglycone. The reaction occurs in two parts as given below. o Firstly, sugar phosphates bind with uridine triphosphate (UTP) to produce sugar— uridine diphosphate sugar complex. o This sugar nucleotide complex reacts with acceptor units (AGLYCONE) in the second reaction which leads to glycoside production. o Once such glycosides are formed, other specific enzymes may transfer another sugar unit in the later reactions in which the glycoside formed in the previous reaction work as an acceptor to provide di-, tri-, or tetra glycosides and so on by subsequent reactions.

JOSE PHILIP G. MAGLALANG, RPh

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PHARMACOGNOSY AND PLANT CHEMISTRY

Classifications • Glycone group • Types of Glycosidic bond • Aglycone group Glycone group • If the glycone group of a glycoside is glucose, then the molecule is a glucoside • If it is fructose, then the molecule is a fructoside • If it is glucuronic acid, then the molecule is a glucuronide Types of Glycosidic bond O-glycosides • Sugar molecule is combined with phenol or –OH group of aglycon • Senna, rhubarb, and frangula N-glycosides • Sugar molecule is combined with N of the –NH (amino group) of aglycon • Nucleosides S-glycosides • Sugar molecule is combined with the S or SH (thiol group) of aglycon • Restricted to isothiocyanate glycosides • Sinigrin C-glycosides • Sugar molecule is directly attached with C—atom of aglycon • Aloin, and cascarosides Aglycone Basis of classification of glycosides containing drugs • Anthraquinone Glycosides • Aglycone part: Anthracene • Mostly employed as CATHARTICS (incorporate the tone of smooth muscle in the wall of the large intestine) • Derivatives are orange in color • Aloe/Aloes o Source: Dried latex of leaves of various species of Aloes, namely ▪ Aloe barbadensis, Miller ▪ A. vera, Linné (Curaçao aloe), known in commercial source ▪ A. ferox Miller ▪ hybrids of this species with A. Africana, Miller and A. spicata Baker, known in commerce as Cape aloe o Family: Liliaceae o Constituents: barbaloin (aloe-emodin) and Isobarbaloin o Uses: Pharmaceutic aid for compound benzoin tincture, burns, abrasions, & skin irritations, and a cathartic.

JOSE PHILIP G. MAGLALANG, RPh

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PHARMACOGNOSY AND PLANT CHEMISTRY

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Frangula or Buckthorn bark o Source: Dried bark of Rhamnnus frangula Linné o Family: Rhamnaceae o Present in Movicol® contains frangula and karaya gum that is used for cathartic and laxatives. o Other Rhamnus species contain anthraquinone glycosides but are not employed in medicine. Rhubarb / Rheum o Source: dried rhizome and root that are deprived of periderm tissues of ▪ Rheum officinale, Bailon or R. pairnaturn Linné (Chinese rhubarb) o Family: Polygonaceae o Constituents: rhem anthrones o Uses: cathartic preparations (the Cathartic action is relatively drastic) Senna or senna leaves o Source: dried leaflet ▪ Alexandria senna (Cassia acutifolia, Delile) ▪ Tinnevelly senna (C. angustifolia Vahl) o Family: Leguminosae o Senna is graded according to the size of the leaf arid the color of the leaflets; blue-green leaves are best, yellowish leaves are poorest. o Constituents: dimeric glycosides whose aglycones are composed of aloe-emodin and/or rhein. sennosides A and B, a pair of optical isomers whose aglvcones are rhein dianthrone (sennidin A and B). o Uses: cathartic. The usual dose is 2 g. Chrysarobin / Goa o Source: obtained from lysogenous cavities in the wood of Andira araroba, Aguiar o Family: Leguminosae o Hot benzene is used to extract this glycoside. o Constituents: chrysophenolanthrone or chrysophenolanthranol o Uses: keratolytic agent and has been employed in the treatment of psoriasis, trichophytosis, and chronic eczema o Only anthraquinone that is NOT used as a cathartic because it is very irritating Cascara sagrada (Sacred bark) o Source: dried bark of Rhamnus purshianus, DeCandolle o Family: Rhamnaceae o It is usually collected at least one year prior to its use. o The name cascara sagrada is Spanish for sacred bark; Rhaninus is the ancient classical name for buckthorn; purshianus was given in honor of the German botanist, Friedrich Pursh o Constituents: The cascara sagrada bark is found to contain two major types of anthracene compounds, namely ▪ Normal O-Glycosides These are based on emodin like structures an constitute about 10 to 20% of the total glycosides

JOSE PHILIP G. MAGLALANG, RPh

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PHARMACOGNOSY AND PLANT CHEMISTRY

Aloin-like C Glycosides These comprise of about 80 to 90% of the total glycosides • The two C-glycosides are known as barbaloin and deoxybarbaloin (or chrysaloin) as given below: • Main active constituents cascarosides A and B are solely based on optical isomers of barbaloin; whereas cascarosides C and D on optical isomers of deoxybarbaloin. o Uses: Cathartic (correction of habitual constipation Restores natural tone of the colon) Danthron or chrysazin o 1,8-dihydroxyanthraquinone o It occurs as an orange-colored crystalline powder that is practically insoluble in water but soluble in alcohol, ether, benzene, and other solvents. o Prepared synthetically from 1,8-anthraquinone potassium disulfonate (Although 18dihydroxyanthraquinone is a natural constituent in certain drugs, it is difficult to isolate in a pure state) o Uses: cathartic drug (The usual dose is 75 to 150 mg.) ▪

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Saponins "Sapo" is Latin name for soap (soap-like) Group of organic compounds that form colloidal solutions with froth when shaken with water even in dilute solution. Aglycone part: sapogenin (Upon hydrolysis they yield an aglycone) Toxic aglycone: Sapotoxin Characteristics: o Soluble in water, alcohol and mixture of them o Form persistent froth with water. o Form precipitate with Ba (OH)2 o Bitter and acrid taste o Cause hemolysis of RBC’s (toxic, especially to cold-blooded animals. Many saponins are used as fish poisons) o Enhance the absorption of other drugs. o Drugs containing saponins are usually sternutatory (an agent or substance that tends to cause sneezing) Biosynthesis: Saponin glycosides are divided into 2 types based on the chemical structure of their aglycones (sapogenins) Triterpenoid saponins Acetate-Mevalonate Pathway o Acetate and mevalonate are duly incorporated into spiroketal steroids as well as pentacyclic triterpenoids. o It is assumed that a branching takes place most probably after the formation of the triterpenoid hydrocarbon squalene

JOSE PHILIP G. MAGLALANG, RPh

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PHARMACOGNOSY AND PLANT CHEMISTRY

Ultimately leads to the spiroketal steroids in one direction and to the pentacyclic triterpenoids Steroidal saponin o Have a spiroketal side chain o Derivatives of steroids o Biogenesis of the steroid nucleus will be discussed in the chapter on steroids. Sources According to the nature of the aglycone, saponins are classified into Steroidal and Triterpenoidal saponins Glycyrrhiza/Licorice o Steroidal glycoside o Sources: dried rhizome and roots of Glycyrrhiza glabra Linné o Family: Leguminosae o Constituents: Glycyrrhizin (glycyrrhizic acid) 50 times as sweet as sugar o Uses: demulcent and expectorant properties, flavoring agent, increase foaminess of bear Masking the taste of bitter drugs such as Aloe, NH4Cl, and quinine, Used for treatment of Addison’s disease (chronic adrenocortical insufficiency) o Contraindication: Patients with cardiac problems & hypertension (increases fluid and sodium retention and promotes potassium depletion) Dioscorea/Yam o Steroidal glycoside o Sources: obtained from the root of Dioscorea spiculiflora and D. floribunda (best source of steroids) o Family: Dioscoreaceae o Constituents: Botogenin and diosgenin o Uses: anti-inflammatory Sarsaparilla o Sources: Smilax regelii o Family: Liliaceae o Constituents: sarsasapogenin and smilagenin o Uses: Flavoring agent in soft drinks along with Glycyrrhiza California soap plant o Sources: Chlorogalum pomeridianum o Family: Liliaceae o Serves as sources of saponins that are used extensively in the industry o Constituents: amolonin o Uses: antidandruff Ginseng o Sources: Asian (Panax ginseng) and American (Panax quinquefolius) o Family: Araliaceae o Constituents: Panaxosides, Ginsenosides, and Chikusetsusaponins o Uses: Aphrodisiac, sexual impotence, anti- diabetes, insomnia, and gastritis o

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JOSE PHILIP G. MAGLALANG, RPh

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PHARMACOGNOSY AND PLANT CHEMISTRY

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Cyanophoric or cyanogenic glycosides Aglycone part: Hydrocyanic acid (they yield either hydrocyanic acid upon hydrolysis or they essentially possess a hydrocyanic acid in the aglycone moiety) Rosaceae being the most prominent one amongst them Derivatives of mandelonitrile (benzaldehyde-cyanohydrin) Flavoring agent (containing drug substances, as such do not exert any specific therapeutic activity, but they are invariably employed as viable pharmaceutical aids, such as: flavoring agents) Biosynthesis Shikimic acid pathway The shikimate pathway provides an alternative route to aromatic compounds, particularly the aromatic amino acids L-phenylalanine, L-tyrosine, and L-tryptophan. This pathway is employed by microorganisms and plants. This amino acid is the starting precursor in synthesis of other glycosides o The first two steps of biosynthetic production of cyanogenic glycoside are catalyzed by a cytochrome P450 enzyme through two successive N-hydroxylations of the amino group of the parent amino acid. o The α-hydroxynitrile (cyanohydrin) is then generated following the decarboxylation and dehydration of aldoxime and nitrile, respectively. o The final step that produces cyanogenic glycoside involves glycosylation of the cyanohydrin moiety, and the process is catalyzed by UDPG glycosyltransferase. Sources: Wild Cherry o Source: dried stem bark of Prunus serotina Ehrhart and prunus virginiana (wild black cherry) o Family: Rosaceae o Constituents: prunasin o Uses: flavored vehicle, sedative expectorant Bitter almond o Source: Prunus amygdalus o Family: Rosaceae o Constituents: Amygdalin o Uses: Arthritis management, Lowers BP, Maintains body pH level. Apricot pits o Source: fruit pits of Prunus armeniaca o Family: Rosaceae o Constituents: Laetrile or Vit B17 (another name for amygdalin. It makes hydrogen cyanide which is changed into cyanide when taken into the body.) o Uses: possibility of controlling sickle cell anemia (tx. of cancer patients)

Isothiocyanate Glycosides Aglycone: Isothiocyanate (The aglycone portion of such glycoside essentially contains isothiocynate residue having sulphur plus nitrogen atoms.) JOSE PHILIP G. MAGLALANG, RPh

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PHARMACOGNOSY AND PLANT CHEMISTRY

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Mostly found in Cruciferae (Latin word meaning “cross bearing” & refers to the shape of the flowers whose petals are arranged in the form of Maltese cross.) Biosynthesis: o Incorporation of acetate to allyl moiety o It has been observed that the aglycone portions of thioglycosides may largely consist of either aliphatic or aromatic derivatives. It is established experimentally that the carboxy-labelled acetate is being incorporated in the allyl moiety of Sinigrin o Allyl moiety Carbon atom bonded to a carbon atom that in turn is doubly bonded to another carbon atom Sources: Black Mustard o Sources: dried ripe seed of varieties of Brassica nigra (Linné) Koch or of B. juncea (Linne) Czerniaew o Family: Cruciferae o Constituents: sinigrin (hydrolyzed by the enzyme myrosin may result to allyl isothiocyanate commonly called mustard oils that is responsible to) o Uses: Local irritant, emetic, rubefacient White mustard o Source: Brassica alba (Linné) Hooker filius o Family: Cruciferae o Constituents: sinalbin (hydrolyzed by the enzyme myrosin may result to ACRINYL ISOTHIOCYANATE that is responsible to) o Uses: Diuretic, Anti-inflammatory

Flavanol Glycosides Aglycone: Flavonoids Usually, visible as yellow pigments in plants Mostly found in citrus plants Best known constituents: o Rutin and Hesperidin ▪ Vitamin P or permeability factors ▪ uses: treatment of capillary bleeding secondary to capillary fragility o Hesperitin, Diosmin, and Naringen/Echinacea ▪ Prophylaxis of common colds o Rutin and Quercetin ▪ Yellow pigment o Isoflavonoids ▪ Found in soya beans, red clover flower ▪ Use as supplements in menopausal period Other sources: Milk thistle o Sources: Silybum marianum o Family: Asteraceae

JOSE PHILIP G. MAGLALANG, RPh

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PHARMACOGNOSY AND PLANT CHEMISTRY

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o o Gingko o o o o

Constituents: Silibinin, Silymarin Uses: Hepatoprotective Sources: Ginkgo biloba Family: Ginkgoaceae Constituents: Gingkolide, Bilobalides Uses: Memory enhancement

Alcohol Glycosides Aglycone: Saligenin Contains free primary alcoholic group. (Yields when a carbon is condensed with an alcohol which loses its hydrogen on its hydroxyl group) Sources: Willow tree o Sources: Salix purpurea and Salix fragilis o Family: Salicaceae o Constituents: Salicin (hydrolyzed by emulsin yielding D-glucose & saligenin (salicyl alcohol)) o Uses: Antirheumatic and Anti-inflammatory Aldehyde glycosides Algycone: Vanillin (methyl protocatechuic aldehyde) (developed during the curing of vanilla beans) Biosynthesis: It has been established that the aromatic nuclei of aldehyde glycosides are usually from the C6C3 precursors formed via the Shikimic Acid Pathway. However, the conversion of cinnamic acid to vanillin is considered to be the most probable route. Sources: Vanilla or vanilla bean o Source: cured, fullgrown, unripe fruit of Vanilla planifolia Andrews (Mexican or Bourbon vanilla) and Vanilla tahitensis J. W. Moore (Tahita vanilla). o Family: Orchidaceae o Constituents: Vanillin o Uses: flavoring agent and as a pharmaceutic aid Lactone glycosides Coumarin glycosides Lactone containing glycosides Sources: Coumarin Lactone of o-hydroxycinnamic acid that can be synthesized readily o Sources: tonka beans (Dipteryx odorata (Aublet) Wilidenow), sweet clover of Melilotus albus Medicus and M. officinalis (Linné) Lamarck, red clover (Trifolium pratense Linne) o Family: Leguminosae JOSE PHILIP G. MAGLALANG, RPh

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PHARMACOGNOSY AND PLANT CHEMISTRY

Uses: antithrombotic, and anticoagulant, flavoring agents (banned by the US FDA due many coumarin-drug interactions) Dicumarol o Drug related to coumarin (first oral anticoagulant) o Sources: Cured leaves and flowering tops of Melilotus officinalis (Linné) Lamarck o Family: Leguminosae o Constituents: Bishydroxycoumarin or dicumarol o Uses: Anticoagulant (usual dose 25 to 200 mg once a day indicated by prothrombin time) Cantharides Spanish flies / Russian flies / Blistering flies Brilliant green with metallic luster o Sources: consists of the dried insect Cantharis vesicatoria (Linné) De Geer o Family: Meliodae o Constituents: cantharidin o Uses: irritant, vesicant, wart removal, and rubefacient o Caution: priapism painful prolonged erection of the penis (If taken internally) Psoralens Photosensitizing furocoumarins that causes phototoxicity o Sources: cremocarps of Bishop’s flower (Ammi majus Linné) o Family: Umbelliferae o Constituents: Methoxsalen, 8-methoxypsoralens, or xanthotoxin o Uses: facilitate repigmentation in idiopathic vitiligo & psoriasis o Contraindication: Keep patients away from sunlight o

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Phenol glycosides The aglycone groups of many of the naturally occurring glycosides are phenolic in character Drugs which yield glucose + hydroquinone Sources: Uva ursi o Sources: dried leaf of Bearberry (Arctostaphylos uva-ursi (Linné) Sprengel) o Family: Ericaceae o Constituents: arbutin o Uses: Astringent and diuretic, whitening agent Gaultherin Sources: Gaultheria procumbens Linné (Wintergreen) Family: Ericaceae Constituents: Gaultherin Uses: use in candies and as a spice, rheumatism, sore muscles

Extraction and Purification • Because of the wide range of physical and chemical properties of glycosides and other constituents associated with them, no common general method for their isolation is recommended

JOSE PHILIP G. MAGLALANG, RPh

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PHARMACOGNOSY AND PLANT CHEMISTRY

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Water, methanol, water-ethanol and ethanol are the most common solvents for extraction of glycosides.

Tests for Glycosides • Borntrager’s Test o Test for Anthraquinone Glycosides o Borntrager’s reagent: Diluted HCl, CCl4 or benzene, and Diluted ammonium o The sample is boiled with dilute sulfuric acid, filtered and to the filtrate benzene, or ether or chloroform is added and shaken well. The organic layer is separated to which ammonia is added slowly. o Positive result: The ammoniacal layer shows pink to red color presences of anthraquinone glycosides • Hemolysis test o Screening test for saponins o A drop of blood on slide + few drops of aq. test solution o Positive result: appearance of ruptured red blood cells or decolorization of the blood agar presence of saponins • Foam test or Froth test o Screening test for saponins o 1 gm of sample drug + 10 to 20 ml of water and well shake o Positive result: Honeycomb or generation of froths greater than 2cm from the surface of the liquid persists after 10 minutes • Ferri Ferrocyanide test o Screening test for cyanogenic glycosides o 1 gm of drug sample + 5 ml of alcoholic KOH → transfer it to aqueous solution of FeSO4 and FeCl3 → keep it on room temperature for10 minutes. → transfer whole solution to 20 % HCl o Positive result: appearance of Prussian blue color presence of cyanogenic glycosides • Liebermann - Burchard Test o Screening test for steroid/triterpenoids o Acetic anhydride is used as solvent and dehydrating agents, and the sulfuric acid is used as dehydrating and oxidizing agent o Positive result: when the solution becomes red or pink, then purple, blue, and finally bluish –green color REFERENCES: • Evans, W. C., Evans, D., & Trease, G. E. (2009). Trease and Evans pharmacognosy (16th ed.). Edinburgh; New York: Saunders/Elsevier. • Tyler, V. E., Brady, L. R., Robbers, J. E., & Claus, E. P. (1976). Pharmacognosy. Philadelphia: Lea & Febiger. • Kar, Ashutosh. (2009). Pharmacognosy And Pharmacobiotechnology. New Age International. • MANOR REVIEW CENTER ...