Glycosides

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Glycosides Tannins
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Glycosides

• Glycosides consist of a sugar residue covalently
  bound to a different structure called the
  aglycone.
• The sugar residue is in its cyclic form and the
  point of attachment is the hydroxyl group of the
  hemiacetal function.
• The sugar moiety can be joined to the aglycone in
  various ways
• Oxygen (O-glycoside)
• Sulphur (S-glycoside)
• Nitrogen (N-glycoside)
• Carbon (Cglycoside)

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• ?-Glycosides and ?-glycosides are distinguished
  by the configuration of the hemiacetal hydroxyl
  group.
• The majority of naturally-occurring glycosides
  are ?-glycosides.
• O-Glycosides can easily be cleaved into sugar and
  aglycone by hydrolysis with acids or enzymes.
• Almost all plants that contain glycosides also
  contain enzymes that bring about their hydrolysis
  (glycosidases).

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• Glycosides are usually soluble in water and in
  polar organic solvents, whereas aglycones are
  normally insoluble or only slightly soluble in
  water.
• It is often very difficult to isolate intact
  glycosides because of their polar character.
• Many important drugs are glycosides and their
  pharmacological effects are largely determined by
  the structure of the aglycone.

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• The term 'glycoside' is a very general one which
  embraces all the many and varied combinations of
  sugars and aglycones.
• More precise terms are available to describe
  particular classes. Some of these terms refer to
  
• the sugar part of the molecule (e.g. glucoside).
• the aglycone (e.g. anthraquinone).
• the physical or pharmacological property (e.g.
  saponin soap-like, cardiac having an action on
  the heart).

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• Modern system of naming glycosides using the
  termination '-oside' (e.g. sennoside).
• Although glycosides form a natural group in that
  they all contain a sugar unit, the aglycones are
  of such varied nature and complexity that
  glycosides vary very much in their physical and
  chemical properties and in their pharmacological
  action.

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1. Anthracene glycosides

• A number of glycosides in which the aglycones are
  anthracene derivatives occur as the
  pharmacologically active constituents of several
  cathartics of plant origin e.g. cascara,
  rhubarb, aloe and senna.
• These anthracene glycosides are sometimes
  referred to as the anthraquinone glycosides or
  the anthraglycosides.

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• These anthraquinone derivatives are glycosides,
  often glucosides or rhamnosides.
• The presence of the sugar residue is a
  prerequisite for the pharmacological effects.
• Anthraquinones are colored substances and many of
  them are used technically as dyes e.g. alizarin.
• Reduced forms of anthraquinones, which exhibit
  keto-enol tautomerism, are often encountered.
• The anthracene derivatives occur in vegetable
  drugs in different forms at different oxidation
  levels like anthraquinones, anthrones,
  anthranols, or oxanthrones.

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Interrelationship of anthraquinone derivatives
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• These anthracene compounds occur in these drugs
  or plant materials in some cases as the aglycones
  of O-glycosides (e.g. frangulin), and in other
  cases as the aglycones of C-glycosides (e.g.
  aloin).
• Biosynthesis natural anthraquinones are
  synthesized either via the acetate-malonate
  pathway (like the medicinally important purgative
  anthraquinones), or they are derived from
  shikimate and mevalonate (like alizarin).

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A. Anthraquinones

• Although anthraquinone is not used extensively in
  medical practice, it is the starting material for
  the preparation of several synthetic laxatives
  and represent the basic structure of a number of
  important laxatives and dyestuffs.
• Borntragers test is often used for their
  detection.
• The derivatives of anthraquinone present in
  purgative drugs may be dihydroxy phenols such as
  chrysophanol, trihydroxy phenols such as emodin
  or tetrahydroxy phenols such as carminic acid.

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B. Anthrones Anthranols

• These reduced anthraquinone derivatives occur
  either free or combined as glycosides.
• They are isomeric and one may be partially
  converted to the other in solution.
• Anthranols are converted upon oxidation into
  anthraquinones. Oxidation takes place in the
  crude drug during storage especially if powdered.
• Schontetens test is often used for anthranols
  (green fluorescence).
• Anthranols and anthrones are the main
  constituents of chrysarobin, a mixture of
  substances.

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C. Oxanthrones

• These are intermediate products between
  anthraquinones and anthranols.
• They give anthraquinones on oxidation with
  hydrogen peroxide.
• An oxanthrone has been reported as a constituent
  of cascara bark.

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D. Dianthrones

• These are compounds derived from two anthrone
  molecules, which may be identical or different.
• They are important aglycones in species of
  Cassia, Rheum and Rhamnus.
• One of the best known is sennoside derived from
  two molecules of glucose and two molecules of
  rhein-anthrone.
• On hydrolysis, sennoside yields the aglycone
  sennidin.

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E. Aloin-type or C-glycosides

• Aloin (Barbaloin) was obtained from species of
  Aloe.
• It is strongly resistant to normal acid
  hydrolysis.
• In aloin, the sugar is joined to aglycone with a
  direct C-C linkage (a C-glycoside).
• Two aloins (A and B) are known and arise from the
  chiral centre at C-10.

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2. Saponin glycosides
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• A group of plant glycosides known as saponins
  share in varying degrees, two common
  characteristics
• (a) They foam in aqueous solution.
• (b) They cause haemolysis of red blood cells.
• The aglycones of the saponins are collectively
  referred to as Sapogenins. The more poisonous
  saponins are often called Sapotoxins.

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• Plant materials containing saponins have long
  been used in many parts of the world for their
  detergent properties for example, in Europe, the
  root of Saponaria officinalis (Fam.
  Caryophyllaceae) and in South America, the bark
  of Quillaia saponaria (Fam. Rosaceae). Such
  plants contain a high percentage of the
  glycosides known as saponins (Latin Sapo, means
  Soap) which are characterized by their property
  of producing a frothing aqueous solution.

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• Properties
• Saponins form colloidal solution in water
  (hydrophilic colloids) which froths upon shaking.
  These substances modify and lower the surface
  tension and therefore foam when shaken. This has
  led to their use to increase the foaming of beer.
• Practical industrial applications of saponins
  include their use in cleaning industrial
  equipment and fine fabrics and as powerful
  emulsifiers of certain resins, fats and fixed
  oils.

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• In general, they have a bitter, acrid taste and
  drugs containing them are usually sternutatory
  (causing or producing sneezing) and irritating to
  the mucous membranes of eyes and nose.
• Characteristic for all saponins is their ability
  to cause haemolysis of red blood corpuscles and
  to destroy them. When injected into the blood
  stream, they are highly toxic.
• When taken by mouth, Saponins are comparatively
  harmless, being not absorbed from the intestinal
  tract. Sarsaparilla, for example, is rich in
  saponins but is widely used in the preparation of
  nonalcoholic beverages.

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• Saponins are toxic especially to cold-blooded
  animals e.g. frogs. Many are used as
  fish-poisons.
• The actual cause of the haemolysis
• The red blood cells carry sterols in their
  membranes, and when brought into contact with
  saponins, the sterols of the RBCs are
  precipitated and the colloidal chemical
  properties of the membrane are so altered as to
  give hemoglobin passage to the surrounding
  medium.
• Saponins have a high molecular weight and their
  isolation in a state of purity presents some
  difficulties.

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• Structure of Saponins
• According to the structure of the aglycone or
  sapogenin, two kinds of saponin are recognized
• The steroidal type (commonly tetracyclic
  triterpenoids, C-27).
• The triterpenoid type (pentacyclic triterpenoids,
  C-30).
• Both of these have a glycosidal linkage at C-3
  and have a common biosynthetic origin via
  mevalonic acid and isoprene units.

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A. Steroidal saponins

• The steroidal saponins are less widely
  distributed in nature than the pentacyclic
  triterpenoid type.
• Steroidal saponins are of great pharmaceutical
  importance because of their relationship to
  compounds such as the sex hormones, cortisone,
  diuretic steroids, vitamin D and the cardiac
  glycosides.
• Examples Diosgenin (Dioscorea sylvatica),
  Sarsapogenin (Smilax sp.).

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B. Pentacyclic triterpenoid saponins

• Triterpenoid saponins my be classified into three
  groups represented by ?-amyrin, ?-amyrin and
  lupeol.
• Examples Primulagenin (Primula sp.), Quillaiac
  acid (Quillaia saponaria) and Glycyrrhetinic acid
  (Glycyrrhiza sp.).

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3. Coumarin glycosides

• The coumarins are shikimate-derived metabolites.
• The majority of the coumarins are oxygenated at
  position C7.
• Coumarins have a limited distribution in the
  plant kingdom and have been used to classify
  plants according to their presence
  (chemotaxonomy).

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• Coumarins are commonly found in the plant
  families Apiaceae, Rutaceae, Asteraceae and
  Fabaceae.
• Some coumarins are phytoalexins and are
  synthesized de novo by the plant following
  infection by a bacterium or fungus.
• Phytoalexins any of a group of compounds formed
  in plants in response to fungal infection,
  physical damage, chemical injury, or a pathogenic
  process. Phytoalexins inhibit or destroy the
  invading agent.

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• These phytoalexins are broadly antimicrobial for
  example, scopoletin is synthesized by the potato
  (Solanum tuberosum) following fungal infection.
• Khellin is an isocoumarin (chromone) natural
  product from Ammi Visnaga (Apiaceae) and has
  activity as a spasmolytic and vasodilator.

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• It has long been known that animals fed sweet
  clover (Melilotus officinalis, Fabaceae) die from
  haemorrhaging. The poisonous compound responsible
  for this adverse effect was identified as
  dicoumarol.
• A number of compounds have been synthesized based
  on the dicoumarol structure, e.g. warfarin, which
  is widely used as anticoagulant.

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• The psoralens are coumarins that possess a furan
  ring and are sometimes known as furanocoumarins.
  e.g. psoralen and bergapten.
• These compounds may be produced by the plant as a
  protection mechanism against high doses of
  sunlight and some coumarins are formulated into
  sunscreens and cosmetics for this purpose.

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4. Flavonoid glycosides

• Biosynthesis
• flavonoids are products from a cinnamoyl-CoA
  (C6C3, precursor from the shikimate pathway)
  starter unit, with chain extension using three
  molecules of malonyl-CoA.
• Flavonoids are therefore of mixed biosynthesis,
  consisting of units derived from both shikimate
  and acetate pathways.

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• The triketide starter unit undergoes cyclization
  by the enzyme chalcone synthase to generate the
  chalcone group of flavonoids. Cyclization can
  then occur to give a pyranone ring containing
  flavanone nucleus, which can either have the
  C2-C3 bond oxidized (unsaturated) to give the
  flavones or be hydroxylated at position C3 of the
  pyranone ring to give the flavanonol group of
  flavonoids. The flavanonols may then be further
  oxidized to yield the anthocyanins, which
  contribute to the brilliant blues of flowers and
  the dark colour of red wine.

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• The flavonoids contribute to many other colors
  found in nature, particularly the yellow and
  orange of petals even the colourless flavonoids
  absorb light in the UV spectrum (due to their
  extensive chromophores) and are visible to many
  insects. A chromophore is the part (or moiety)
  of a molecule responsible for its color.
• It is likely that these compounds have high
  ecological importance in nature as colour
  attractants to insects and birds as an aid to
  plant pollination.

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• Certain flavonoids also markedly affect the taste
  of foods for example, some are very bitter and
  astringent such as the flavanone glycoside
  naringin, which occurs in the peel of grapefruit
  (Citrus paradisi). Interestingly. the closely
  related compound naringin dihydrochalcone, which
  lacks the pyranone ring of naringin, is
  exceptionally sweet, being some 1000 times
  sweeter than table sugar (sucrose).

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• the flavonoids have important dietary
  significance because, being phenolic compounds,
  they are strongly antioxidant.
• Many disease states are known to be exacerbated
  by the presence of free radicals such as
  superoxide and hydroxyl, and flavonoids have the
  ability to scavenge and effectively mop up
  these damaging oxidizing species.

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• Foods rich in this group have therefore been
  proposed to be important in ameliorating diseases
  such as cancer and heart disease (which can be
  worsened by oxidation of low-density
  lipoprotein) quercetin, a flavonoid present in
  many foodstuffs, is a strong antioxidant.
  Components of milk thistle (Silybum marianum), in
  particular silybin, are antihepatotoxins
  extracts of milk thistle are generally known as
  silymarin.

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Some action and therapeutic uses of flavonoids

• Many flavonoid containing plants are
• Diuretic.
• Antispasmodic.
• Diaphoretic.
• Increase tensile strength of capillary walls.
• Free radical scavengers.

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5. Cyanogenetic glycosides(Cyanide glycosides)

• Cyanogenesis is the ability of certain living
  organisms, plants in particular, to produce
  hydrocyanic acid (HCN, prussic acid).
• Cyanogenesis in plants is a chemical defense
  mechanism against organism damaging or feeding on
  plant tissues and lead to release of HCN gas,
  which is toxic.
• They are distributed in over 2000 plant species
  belonging to 110 families.

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• These compounds, in presence of enzymes such as
  ?-glucosidase, lose their sugar portion to form a
  cyanohydrin which, in the presence of water and
  hydroxynitrile lyase, can undergo hydrolysis to
  give benzaldehyde and the highly toxic hydrogen
  cyanide (HCN).
• The sugar portion of the molecule may be a
  monosaccharide or a disaccharide such as
  gentiobiose or vicianose. If a disaccharide,
  enzymes present in the plant may bring about
  hydrolysis in two stages, as in the case of
  amygdalin.

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• They are derivatives of ?-hydroxynitrile or
  2-hydroxynitrile (cyanohydrins).
• In all cases the first sugar attached to the
  aglycone is ?-D-glucose.
• R1 and R2 are often different residues resulting
  in pairs of C-2 epimers.
• (Epimers are diastereomers that differ in
  configuration at only one of their stereogenic
  centers).

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• Most cyanogenetic glycosides are biosynthetically
  derived from the amino acids valine, leucine,
  isoleucine, tyrosine or phenylalanine.
• Cyanogenetic glycosides are easy to detect with a
  strip of filter paper impregnated with reagents
  able to give a color reaction with the
  hydrocyanic acid released upon crushing the plant
  material (e.g., picric acid/sodium carbonate or
  benzidine/cupric acetate).
• Although hydrocyanic acid is a violent poison, it
  is important to remember that oral intake of
  cyanogenetic drugs does not necessarily cause
  severe intoxication, this is because the range of
  dangerous concentrations (0.5-3.5 mg/kg) can only
  be achieved by rapid and massive ingestion of
  plant parts rich in cyanogenetic glycosides.

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• Examples
• Amygdalin in bitter almonds (Prunus amygdalus).
  It is biosynthetically derived from
  phenylalanine.
• Linamarin in linseed (Linum usitatissimum). It is
  biosynthetically derived from valine.

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6. Steroidal cardioactive glycosides

• Cardiac glycosides are a group of natural
  products characterized by their specific effect
  on myocardial contraction and atrioventricular
  conduction.
• In large doses they are toxic and bring about
  cardiac arrest in systole, but in lower doses
  they are important drugs in the treatment of
  congestive heart failure.
• They have a diuretic activity. Since, the
  improved circulation tends to improve renal
  secretion, which relieves the edema often
  associated with heart failure.

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? Distribution in nature

• Cardiac glycosides occur in small amounts in the
  seeds, leaves, stems, roots or barks of plants of
  wide geographical distribution, particularly of
  the Fam. Apocyanaceae (e.g. seeds of
  Strophanthus, roots of Apocynum and fruits of
  Acokanthera) others are found in the
  Scrophulariaceae (e.g. leaves of Digitalis sp.),
  Liliaceae (e.g. scales of the bulbs of Urginea
  and Convallaria), and Ranunculaceae (Adonis).
• Cardiac glycosides are also found in animals only
  in exceptional cases Bufadienolides occur in
  toads (Bufo).

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? Structure of glycosides

• The structure comprise a steroidal aglycone of
  the (C23) cardenolide type or of the (C24)
  bufadienolide type, and a sugar moiety, most
  often an oligosaccharide.

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A. Structure of the aglycones

• All of the aglycones have in common the classic,
  tetracyclic, steroidal nucleus.
• The A, B, C and D rings normally have a
  cis-trans-cis configuration or less often, a
  trans-trans-cis configuration.
• Also common to all the aglycones is the presence
  of two hydroxyl groups one is a 3? secondary
  alcohol, the other is a 14? tertiary alcohol.
• All of the aglycones have a ? constituent at
  C-17 an ?,?-unsaturated lactone.

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• The size of the lactone ring distinguishes two
  groups of aglycones the C23 cardenolides with an
  ?,?-unsaturated ?-lactone ( butenolide) and the
  C24 bufadienolides with a di-unsaturated
  ?-lactone ( pentadienolide).

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B. Structure of the sugar moiety

• The sugar moiety is generally linked to the
  aglycone through the hydroxyl group at C-3.
• The majority of the saccharides found in cardiac
  glycosides are highly specific
• 2,6-dideoxyhexoses, e.g. D-digitoxose
• 2,6-dideoxy-3-methylhexoses, e.g. D-diginose
• 6-deoxyhexoses, e.g. L-rhamnose
• 6-deoxy-3-methylhexoses, e.g. D-digitalose
• Hexose, e.g. glucose (when these is a glucose
  unit, it is always terminal).
• The sugars can modify the activity (potency,
  toxicity), the solubility, the diffusion through
  membranes, the rate of absorption and
  transportation of the glycosides.

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C. Structure-Activity Relationships (SAR)

• The cardiac activity is linked to the aglycone.
• The sugar moiety does not participate directly in
  the activity, but its presence enhances the
  activity and modulates it by modifying the
  polarity of the compound.
• The presence of a certain number of structural
  elements is required for, or at least favorable,
  to the activity
• The lactone at C-17, and it must be in the ?
  configuration.
• The configuration of the rings. The activity is
  maximized when the A, B, C and D rings are in the
  cis, trans, cis configuration. The C and D rings
  must be cis fused.
• The substituents. The inversion of the
  configuration at C-3 diminishes the activity, but
  3-deoxy compounds are not completely inactive.

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? Biosynthetic origin

• Aglycone of the cardiac glycosides are derived
  from mevalonic acid but the final molecules arise
  from a condensation of a C21 steroid with a C2
  unit (the source of C-22 and C-23).
  Bufadienolides are condensation products of a C21
  steroid and a C3 unit.

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? Color reactions

• They can be due to the sugars or to the aglycone
• Color reactions of the sugars. The only color
  reactions of the sugars that are of interest are
  those specific to 2-deoxyhexoses. e.g.
  Keller-Kiliani test.
• Color reactions of the aglycones (steroidal
  nucleus). These are positive with any compound
  containing a steroidal nucleus including
  cardenolides or bufadienolide
• Antimony trichloride (SbCl3)
• Liebermann's test (for bufadienolides)

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• Color reactions of the aglycones (lactone ring).
• These are characteristic for cardenolides having
  a five-membered lactone ring
• Legal's test
• Raymond's test
• Kedde's test
• Baljet's test

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Pharmacological properties

• Cardiac glycosides increase the force and speed
  of contraction of the heart. In patients with
  cardiac insufficiency, this positive inotropic
  effect translates into 1an increase in cardiac
  output, 2an increase in cardiac work capacity
  without any increase in oxygen consumption, 3a
  decrease in heart rate, and, indirectly, 4a
  decrease in arterial resistance. (MOA) The
  glycosides are thought to act at the membrane
  level, by inhibition of the Na-K ATPase, which
  would result in an increase of the intracellular
  calcium ion concentration.

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Therapeutic indications

• Cardiac glycosides are currently indicated for
• Cardiac insufficiency with low output (generally
  in combination with diuretics), particularly when
  there is atrial fibrillation.
• Supraventricular rhythm abnormalities to slow
  down or decrease atrial fibrillation or flutter.

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Examples

• Strophanthus glycosides
• The name Strophanthus is derived from the Greek
  strophos (a twisted cord or rope) and anthos (a
  flower).
• e.g. Strophanthus kombe
• The principle glycosides are
• K-strophanthoside
• K-strophanthin-?
• Cymarin

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• Squill glycosides
• Urginea maritima (L.)
• 0.1 ? 2.4 total bufadienolides, ?15
  glycosides
• White variety average 0.2-0.4
• proscillaridin A, scillaren A, glucoscillaren A
  (aglycone scillarenin)
• scilliphaeoside, scilliglaucoside
• Red variety lt 0.1
• scilliroside and glucoscilliroside (aglycone
  scillirosidin) proscillaridin A and scillaren A
  as in the white variety

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Pharmacological properties of squill

• White squill
• it is an expectorant, but it also possesses
  emetic, cardiotonic (proscillaridin A), and
  diuretic properties.
• Red squill
• it is used as a rat poison (scilliroside),
  because rodents lack the vomiting reflex, which
  makes red squill particularly lethal to these
  animals.

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• Digitalis glycosides
• Several species of Digitalis yield
  pharmacologically active principles. The most
  important of these species are Digitalis purpurea
  and Digitalis lanata.
• Digitalis purpurea folium (Red foxglove leaves)
• 0.15 ? 0.4 total cardenolides, ? 30 glycosides
  Purpurea glycosides A and B (?60), digitoxin
  (?12), gitoxin (?10) and gitaloxin (?10).
• Digitalis lanata folium (White foxglove leaves)
• 0.5 ? 1.5 total cardenolides, ? 60 glycosides
  Lanatosides A and C (?50), lanatosides B, D, E
  as well as digoxin and digitoxin.

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• Digitoxin is a cardiotonic glycoside obtained
  from D. purpurea, D. lanata.
• It is the most lipid-soluble of the cardiac
  glycosides used in therapeutics.
• The major pharmacokinetic parameters for
  digitoxin include complete oral absorption, which
  distinguishes it from other cardiac glycosides.
• Digitoxin may be indicated in patients with
  impaired renal function.

• Digoxin is the most widely used of the
  cardiotonic glycosides, and it is obtained from
  the leaves of D. lanata.
• It is a highly potent drug and should be handled
  with exceptional care.
• Digoxin tablets are 60 to 80 absorbed.
• Digoxin is indicated when the risk of digitalis
  intoxication is great, since it is relatively
  short-acting and rapidly eliminated when compared
  with digitoxin.

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Digitalis purpurea
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7. Tannins

• Historically, the importance of tannin-containing
  drugs is linked to their tanning properties, in
  other words their ability to transform fresh
  hides into an imputrescible material leather.
• Tannins are "phenolic natural products that
  precipitate proteins from their aqueous
  solutions".

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• The consequence of tanning is the formation of
  bonds between the collagen fibers in the hide,
  which imparts resistance to water, heat, and
  abrasion. This capability of tannins to combine
  with macromolecules explains why they precipitate
  cellulose, pectins, and proteins it also
  explains their characteristic astringency and
  tartness by precipitating the glycoproteins
  contained in saliva, tannins make the latter lose
  its lubricating power.
• Most true tannins have molecular weights from
  about 1000 ? 5000.

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Pseudotannins

• They are compounds of lower molecular weight than
  true tannins and they do not respond to the
  goldbeater's skin test.
• Examples of drugs containing Pseudotannins are
• Gallic acid Rhubarb
• Catechins Guarana, Cocoa
• Chlorogenic acid Mate, Coffee
• Ipecacuanhic acid ipecacuanha

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Function of tannins in plants

1. Tannins are considered the source of energy
   through their oxygen content.
2. They serve as a protective to the plant (plant
   antiseptics).
3. They may have function in respiratory activity,
   i.e. in the mechanisms of hydrogen transfer in
   plant cells.
4. Tannins play an important part in the acceptance
   of many foods and beverages by consumers e.g.
   tea, cocoa.

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Classification of tannins

• In higher plants, two groups of tannins are
  generally distinguished, which differ by their
  structure, as well as their biosynthetic origin
  hydrolysable tannins and condensed tannins.
• Hydrolysable tannins
• Hydrolysable tannins are esters of a sugar (or
  related polyol) and of a variable number of
  phenolic acid molecules.

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• The sugar is most generally glucose.
• The phenolic acid is either gallic acid, in the
  case of gallitannins, or Ellagic acid, in the
  case of the tannins conventionally referred to as
  ellagitannins.
• Ellagic acid can arise by lactonization of
  hexahydroxydiphenic acid ( HHDP) during chemical
  hydrolysis of the tannin.
• Hydrolysable tannins were formerly known as
  pyrogallol tannins, because on dry distillation
  gallic acid and similar components are converted
  into pyrogallol.

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• Biosynthetically, gallic acid (
  3,4,5-trihydroxybenzoic acid) arises from the
  metabolism of shikimic acid.
• Examples of drugs containing Hydrolysable
  tannins
• Gallitannins rhubarb, cloves, Chinese galls,
  Turkish galls, hamamelis, chestnut and maple.
  Ellagitannins pomegranate rind, pomegranate
  bark, eucalyptus leaves, and oak bark.

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• Condensed tannins (proanthocyanidins)
• Condensed tannins or proanthocyanidins are
  polymeric flavans. They consist of flavan-3-ol
  units linked together by carbon-carbon bonds,
  most often 4?8 or 4?6, which result from coupling
  between the electrophilic C?4 of a flavanyl unit
  from a flavan-4-ol or flavan-3,4-diol and a
  nucleophilic position (C-8, less commonly C-6) of
  another unit, generally a flavan-3-ol.
• Unlike hydrolysable tannins, these are not
  readily hydrolyzed to simpler molecules and they
  do not contain a sugar moiety.

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• Biosynthetically, flavonoids are derived from
  acetate and shikimate pathways.
• Condensed tannins occur due to polymerization
  (condensation) reactions between flavonoids.
• The polymers may include up to 50 monomer units.
• On treatment with acids or enzymes condensed
  tannins are converted into red insoluble
  compounds known as phlobaphenes. Phlobaphenes
  give the characteristic red colour to many drugs
  such as red cinnamon bark.

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• Examples of drugs containing Condensed tannins
• Some drugs (e.g. tea, hamamelis leaves and
  hamamelis bark) contain both hydrolysable and
  condensed tannins. The following are rich in
  condensed tannins.
• (1) Barks cinnamon, wild cherry, cinchona,
  willow, acacia, oak and hamamelis
• (2) Roots and rhizomes krameria (rhatany) and
  male fern
• (3) Flowers lime and hawthorn
• (4) Seeds cocoa, guarana, and kola
• (5) Leaves hamamelis, hawthorn and tea,
  especially green tea
• (6) Extracts and dried juices catechu, acacia
  and mangrove cutches

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Properties and tests of tannins

• Tannins are soluble in water, dilute alkalis,
  alcohol, glycerol and acetone, but generally only
  sparingly soluble in other organic solvents.
• Solutions precipitate heavy metals, alkaloids,
  glycosides and gelatin.
• With ferric salts, gallitannins and ellagitannins
  give blue-black precipitates and condensed
  tannins brownish-green ones. If a very dilute
  ferric chloride solution is gradually added to an
  aqueous extract of hamamelis leaves (which
  contains both types of tannin), a blue colour is
  produced which changes to olive-green as more
  ferric chloride is added. Other useful tests are
  the following

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• Goldbeater's skin test
• Soak a small piece of goldbeater's skin in 2
  hydrochloric acid rinse with distilled water and
  place in the solution to be tested for 5 min.
  Wash with distilled water and transfer to a 1
  solution of ferrous sulphate. A brown or black
  colour on the skin denotes the presence of
  tannins. Goldbeater's skin is a membrane prepared
  from the intestine of the ox and behaves
  similarly to an untanned hide.

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• Gelatin test
• Solutions of tannins (about 0.5-1 ) precipitate
  a 1 solution of gelatin containing 10 sodium
  chloride. Gallic acid and other pseudotannins
  also precipitate gelatin if the solutions are
  sufficiently concentrated.
• Phenazone test
• Test for catechin
• Test for chlorogenic acid

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Medicinal and biological properties

• The applications of tannin-containing drugs are
  limited, and result from their affinity for
  proteins.
• Tannin-containing drugs will precipitate protein
  and have been used traditionally as styptics and
  internally for the protection of inflamed
  surfaces of mouth and throat.
• They act as antidiarrhoeals and have been
  employed as antidotes in poisoning by heavy
  metals, alkaloids and glycosides.

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Gall-oak
sumac