alkaloids.ppt
- 1. Alkaloids 11/6/2023 1 Dr. Quazi Majaz A., Associate Professor & Head, Department of Pharmacognosy, Ali Allana College of Pharmacy, Akkalkuwa
- 2. The term “alkaloid” (alkali-like) is commonly used to designate basic heterocyclic nitrogenous compounds of plant origin that are physiologically active and shows pharmacological action in small dose.
- 3. Deviation from Definition • Basicity: Some alkaloids are not basic e.g. Colchicine, Piperine, Quaternary alkaloids. • Nitrogen: The nitrogen in some alkaloids is not in a heterocyclic ring e.g. Ephedrine, Colchicine, Mescaline. • Plant Origin: Some alkaloids are derived from Bacteria, Fungi, Insects, Frogs, Animals. • Biosynthesis: Some alkaloids are not derived from amino acids e.g purine, steroidal alkaloid .
- 4. These are the organic products of natural or synthetic origin which are basic in nature and containing one or more nitrogen atom normally of heterocyclic nature and posses pharmacological action in small dose on human and animals
- 6. Physical Properties: I- State: • Most alkaloids are crystalline solids. • Few alkaloids are amorphous solids e.g. emetine. • Some are liquids that are either: Volatile e.g. nicotine and coniine, or Non-volatile e.g. pilocarpine and hyoscine. II- Color: The majority of alkaloids are colorless but some are colored e.g.: • Colchicine and berberine are yellow. • betanidine is orange.
- 7. III- Solubility: Both alkaloidal bases and their salts are soluble in alcohol. Generally, the bases are soluble in organic solvents and insoluble in water Exceptions: Bases soluble in water: caffeine, ephedrine, codeine, colchicine, pilocarpine and quaternary ammonium bases. Bases insoluble or sparingly soluble in certain organic solvents: morphine in ether, theobromine and theophylline in benzene. Salts are usually soluble in water and, insoluble or sparingly soluble in organic solvents. Exceptions: Salts insoluble in water: quinine monosulphate. Salts soluble in organic solvents: lobeline and apoatropine hydrochlorides are soluble in chloroform
- 8. IV- Isomerization • Optically active isomers may show different physiological activities. l-ephedrine is 3.5 times more active than d-ephedrine. l-ergotamine is 3-4 times more active than d-ergotamine. d- Tubocurarine is more active than the corresponding l- form. • Quinine (l-form) is antimalarial and its d- isomer quinidine is antiarrythmic. • The racemic (optically inactive) dl-atropine is physiologically active.
- 9. Distribution in Plant All Parts e.g. Datura. Barks e.g. Cinchona Seeds e.g. Nux vomica Roots e.g. Aconite Fruits e.g. Black pepper Leaves e.g. Tobacco Latex e.g. Opium
- 10. QUALITATIVE CHEMICAL TESTS FOR ALKALOIDS 1. Dragendorff’s test: To 2–3 ml of the solution add few drops of Dragendorff’s reagent (potassium bismuth iodide solution). An orange brown precipitate is formed. 2. Mayer’s test: To 2–3 ml of the drug add few drops of Mayer’s reagent (potassium mercuric iodide solution). White brown precipitate is formed. 3. Hager’s test: To 2–3 ml of the alkaloid solution add few drops of Hager’s reagent (saturated solution of picric acid). Yellow precipitate is formed. 4. Wagner’s test: To 2–3 ml of the alkaloid solution add few drops of Wagner’s reagent (iodine– potassium iodide solution). Reddish brown precipitate is formed.
- 11. Powdered plant material Defatted with non-polar solvent Defatted plant material Moist with water and treated with NH3, Dil. Lime solution (Free Alkaloid) Extracted with organic solvent like chloroform, ether Extract, Concentrate it Dissolved in Dil. Acid (Alkaloidal salt) Aqueous phase Organic phase impurities Basified with ammonia or sodium Bi-carbonate or Dil. KOH Aqueous phase Organic phase(Free Alkaloid) Evaporate to dryness Crude Alkaloids Extraction of alkaloids 1. Stass otto method
- 12. Powdered Crude material Defatted with non-polar solvent Defatted Crude material Extract with methanol Methanol Extract Concentrate Dissolve in water and Acidified it upto pH 2 (Alkaloidal salt) Steam Distillation to remove traces of methanol Stand for several days in refrigerator OR boiled with paraffin Filter Filtrate Shake with organic solvent like chloroform or ether Aqueous phase (Alkaloidal salt) Organic phase Basified with ammonia or sodium Bi-carbonate or Dil. KOH Aqueous phase Organic phase Evaporate to dryness Crude Alkaloids Extraction of alkaloids 2. Manske’s method
- 13. Purification of Alkaloids 1. Direct crystallization from solvent 2. Repeated acid base treatment 3. Fractional crystallization 4. Chromatographic techniques 5. Gradient pH technique Ephedrine & Pseudoephedrine Oxalates Crystallization from water Ephedrine Oxalate Crystals Pseudoephedrine Oxalate Solution Atropine & Hyoscyamineine Oxalates Crystallization from Acetone/Ether Atropine Oxalate Crystals Hyoscyamine Oxalate Solution
- 14. A) True alkaloids Sr. no. Type Structure Examples 1. Pyrrole and pyrrolidine N H N H e.g. Hygrine, coca species 2. Pyiridine and piperidine N N H e.g. Arecoline, anabasine, lobeline, conine, trigonelline 3. Pyrrolizdine N e.g. Echimidine, senecionine, seneciphylline 4. Tropane N e.g. Atropine, hyoscine, hyoscyamine, cocaine, pseudopelletirine 5. Quinoline N e.g. Quinine, quinidine, cinchonine, cupreine, camptothecine 6. Isoquinoline N e.g.Morphine, codeine, emetine, cephaline, narcotine, narceine, d- tubocurarine Classification of alkaloids Chemical classification
- 15. 7 Indole N H e.g. Erotamine, ergotametriene, reserpine, vincristine, vinblastine, strychnine, brucine 8 Imidazole N N H e.g. Pilocrpine, isopilocarpine, pilosine 9 Norlupinane N e.g. Cystisine, laburinine 10 Piporphine (reduced isoquinoline napthalene) N e.g. Boldine
- 16. B) PROTOALKALOID 1. Alkyalamine HO NH Ephedrine, Pseudoephedrine C) Pseudoalkaloid 1. Purine N N N HN e.g. Caffeine, thophylline, theobromine 2. Steroidal e.g. Solanidine, conessine, protoveratrine 3. Diterpene C20H32 e.g. Aconitine, aconine, hypoaconine
- 17. Pharmacological classification 1. Narcotic analgesic e.g.Morphine 2. Antimalerial e.g. Quinine 3. Reflux excitability e.g.Strychnine 4. Respiratory stimulant e.g.Lobeline 5. Neuralgia e.g. Aconitine 6. Oxytocic e.g. Erogotometrine 7. Bronchodilator e.g. Ephedrine, vasicine 8. Anticholinergic e.g. Atropine 9. CNS stimulant e.g. Caffeine 10. Antitussive e.g. Codeine 11. Antiarrythmic e.g.Quinidine 12. Antihypertensive e.g. Reserpine 13. Anticancer e.g. Vincristine 14. Antiglucoma e.g. Pilocarpine
- 18. Catharanthus ( Vinca) Synonyms- Vinca rosea, Catharanthus, periwinkle. Biological Source- Vinca is the dried entire plant of Catharanthus roseus Linn., belonging to family Apocynaceae.
- 19. Macroscopical characters: Type – Annular or perennial herb; Size – 0.5 to 1 meter length; Leaves – Ovate, oblong, glossy above glaucous below; Flowers – 2 to 3 in cymes, axillary and terminal clusters. Bases on flower colour, three varieties are known namely – alba-white, ocillata-white with pink or carmine red eyes and roseus -with rose coloured flowers. Fruit- a follicle, cylindrical and many seeded. Taste – Bitter; Odour – slight
- 21. Chemical constituents: Indole and indoline alkaloids: Ajmalicine Lochnerine Serpentine and Tetrahydro alstonine: Dimeric Indole bases of monoterpene type Vinblastin Vincristin.
- 22. Uses Vinblastin is an antitumour alkaloid used in the treatment of Hodgkin’s disease. Vincristine is a cytotoxic compound and used to treat leukaemia in children. Vinca is used in herbal practice for its astringent and tonic properties in menorrhagia and in haemorrhages. The flowers of the Periwinkle are gently purgative, but lose their effect on drying.
- 23. Rauwolfia* Synonyms- sarpagandha, Biological source: Rauwolfia consists of the dried roots and rhizomes of Rauwolfia serpentina Benth. It contains not less than 0.15% of reserpine belong to Family Apocynaceae.
- 24. Cultivation: •Its grows spontaneous in tropical forests (temp,10°C to 40°C) which are humid in summer at an altitude up to about 1200 metres. • Rauwolfia plants cannot tolerate temperature below 5°C. •For cultivation rain must be enough and abundant in summer or it should have good irrigation. •Propagation is carried out by planting seeds, root-culture or stem-cutting. Seed propagation gives better yield of root in spite of the fact some seeds are weak in germination.
- 25. Therefore cultivation of rauwolfia is usually carried out by seed propagation. Immersing them in saline eliminates sterile seeds. Rauwolfia grows well in clays, acidic (pH-4 to 6) and well-manure soil. Ploughing must be deep for facilitating the development of the roots. Sterile seeds are light, float and are separated. Fertile seeds sink and are utilized. Fresh seeds germinate more and preferably fresh seeds are used. In vegetative propagation especially in root-cuttings, development of roots is better if growth hormones are used.
- 26. Collection: They are collected in October-November after hot and dry period. In Indian Pharmacopoeia collection of roots of 3 to 4 years old plants is mentioned but in culture it is found that roots of 2 years old plants are equally good. For collection of roots plants are dug out, aerial parts are removed and roots are separated. Roots are washed and dried in air till moisture is about 10 to 12%. Roots should be stored protected from light.
- 28. Microscopical characters (T.S.): T. S. of the root presents a circular outline with typical stratified cork and other secondary features. Following are the tissues seen from the periphery to the center.
- 29. Periderm: a. Cork (Phellum): Stratified, consists of alternating bands- of smaller, suberized and un-lignified cell up to 8 to 10 raw in radial depth- larger, suberized but lignified cell upto 5 to 7 raw in radial depth. b. Phellogen: Indistinct but is seen as a narrow layer of thin walled cells, c. Phelloderm: 5 to 7 layers, immediately below the phloem, cell is arranged in the radial rows whereas away from phloem, cell is oval and has intercullar spaces. Phelloderm contains abundant starch grains (with triradiate hilum) and typical twin prisms of calcium oxalate.
- 30. Secondary phloem: Is transverse by conspicuous medullary rays. Phloem consists of sieve tubes, companion cells and phloem parenchyma. Starch grains and calcium oxalate prism occurs throughout the phloem tissue. Secondary xylem: It is also transverse by well develop medullary rays. Xylem consists of vessels, wood fibres and lignified parenchyma.
- 31. Medullary rays: It runs radially from the center to the cortex through the phloem. Rays in the xylem region are lignified, pitted and are 1 to 5 cells wide although uniseriate rays are prominent. In the phloem region the ray cells are not lignified. Starch and typical oxalate prisms are in the medullary ray cells.
- 32. Chemical constituents: Alkaloids- Indole alkaloids (1.5 or 3%) present. Weakly basic Indole type (pH 7 to 7.5) Reserpine group – Reserpine, Rescinnamine, deserpidine. Tertiary indoline alkaloids (pH-8). Ajmaline group- Ajmaline and Ajmalicine. Strongly basic anhydronium bases (pH-11). Serpentine group – Serpentine, Serpentinine and Alsotonine.
- 34. Uses: 1. Rauwolfia is used as hypotensive and tranquillizer. 2. Reserpine being the main alkaloid is responsible for the activity and is used in anxiety condition and other neuropsychoiatric diseases. 3. Sedative – calm down activities and excitement (reserpine group). 4. Stimulates the central of peripheral nervous systems (Ajmaline group). 5. The decoction of root is used to increase uterine contraction in difficult cases. 6. The extract is used for intestinal disorders and as anthelmintic bitter tonic and febrifuge.
- 35. Belladonna Synonym- Belladonna leaf Biological source- It consist of dried leaves of or the leaves and the arial part of the plant Atropa beladona, belong to family Solanaceae Morphological characters- Color- leaves- green to brownish green flower- purple to yellowish brown Fruits- green to brown
- 36. Odour- slight and characterists Taste- bitter and acrid Size- leaves- 5 to 25 cm long and 2.5 to 12 cm widw Shape- leaves are ovate Chemical const- The active agents in belladonna, atropine, hyoscine (scopolamine), and hyoscyamine
- 37. Uses- Belladonna has been used in herbal medicine for centuries as a pain reliever, muscle relaxer, and anti-inflammatory, and to treat menstrual problems, peptic ulcer disease, histaminic reaction, and motion sickness
- 38. Chemical test- Vitali-Morin reaction- 1. Tropane alkaloid treated with fuming nitric acid followed by evaporation to dryness and addition of methanolic potassium hydroxide solution to an acetone solution of nitrated residue. Violet coloration take place. Tr. Alk.+ Fuming Nitric acid------Evap. To dry+ met. KOH+ acetone ----- violet colouration. 2. On addition of silver nitrate to solution of hyoscine hydrobromide, yellowish white ppt is formed, which is insoluble in nitric acid, but soluble in dil. Ammonia. Hyoscine + Silver nitrate---------- yellow white ppt
- 39. OPIUM •Synonyms: Raw Opium, Crude Opium •Biological Source: Opium is the dried milky latex obtained by incision fromthe unripe capsules of Papaver somniferum, belonging to family Papaveraceae. Characteristics Opium occurs in rounded or flattened mass which is 8–15 cm in diameter and weighing from 300 g to 2 kg each. The external surface is pale or chocolate-brown, texture is uniform and slightly granularand odour is characteristic; taste is bitter and distinct.
- 49. •Chemical Constituents •Opium contains about 19 alkaloids among which morphine is the most important base. The alkaloids are combined with meconic acid. The other alkaloids isolated from the drug are codeine, narcotine, thebaine. noscapine, narceine and papaverine.
- 52. Uses •Opium and morphine have narcotic, analgesic and sedative action and used to relieve pain, diarrhoea dysentery and cough. Poppy capsules are astringent, somniferous, soporific, sedative and narcotic.