Purine Alkaloids PDF

5-Purine Alkaloids Purines are derivatives of a heterocyclic nucleus consisting of a six-membered Pyrimidine ring fused to a five-membered Imidazole ring. Purines are Psudo alkaloids (Are not derived from amino acids but have nitrogen in a heterocyclic ring) (True alkaloid- protoalkaloid- pseudoalka...

5-Purine Alkaloids Purines are derivatives of a heterocyclic nucleus consisting of a six-membered Pyrimidine ring fused to a five-membered Imidazole ring. Purines are Psudo alkaloids (Are not derived from amino acids but have nitrogen in a heterocyclic ring) (True alkaloid- protoalkaloid- pseudoalkaloid) Purine Alkaloids xanthine Theophylline Theobromine caffeine They are all methyl derivatives of xanthine  5-Purine Alkaloids Occurrence, Characters and Activities Occurrence Theobroma cacao tree, Folia Theae (Tea Lea), Thea sinensis (Chinese Tea) (Family Teas; Theaceae). Sеmina Coffeae (Fam. – Rubiaceae) Coffeine [Tea leaves (2- 5%), Coffee seeds (1-2 %), Cola leaves (2- 3%), Gurana seeds (2.5- 5 %) and Cacao seeds, (0.2- 0.5 %)]. Characters These alkaloids are weak bases, they give no precipitate with Mayer's reagent. They have Amphoteric Character Peculiar solubility in warm water and in chlorinated solvents. Caffeine :- completely Water soluble. Sublimable. Theobromine: Sparingly soluble in water. Sublimable. Amphoteric Theophylline: - Sparingly soluble in water  5-Purine Alkaloids Occurrence, Characters and Activities Activities Caffeine: stimulates CNS and has a weak diuretic action. Theobromine: Has little CNS stimulant action, but has more diuretic activity, and has smooth muscle relaxant effect. Theophylline: Has low CNS stimulant action and is an effective diuretic, but it is an important smooth muscle relaxant & used for relief of bronchial spasms Caffeine is metabolized in the liver by the cytochrome P450 oxidase enzyme system into three metabolic dimethylxanthines, which each have their own effects on the body Paraxanthine (84%): Increases lipolysis, leading to elevated glycerol and free fatty acid levels. Theobromine (12%): Dilates blood vessels and increases urine volume. Theophylline (4%): Relaxes smooth muscles of the bronchi, and is used to treat asthma. Each of these metabolites is further metabolized and then excreted in the urine. Side effects: tacchycardia ,Epigastric pain ,Nausea, Vomiting , Headaches , Nervousness Chemical structure of Caffeine and the Insomnia ,tremors three primary metabolites that it is metabolized into inside the liver  5-Purine Alkaloids Color tests  Murexide test: (caffeine, theobromine and theophylline). Crystals of caffeine + drops of concentrated HCl and traces of KClO3 →evaporated on water bath → red color is produced wich turns to violet on exposure to ammonia vapor.  Tannic acid test: (caffeine and theophylline): A concentrated solution of the alkaloid + tannic acid → white precipitate is obtained that dissolves in excess of the reagent.  Ferrous sulfate test: (theobromine): To a solution of the alkaloid + drops of concentrated HCl + few drops of Br2 water + a drop of FeSO4 + few drops of ammonia → Blue color. Typical/hetrocyclic alkaloids 6-Alkaloids of the Pyridine nucleus 10  6-Alkaloids of the Pyridine nucleus This group of Alkaloids Derived from Aspartic Acid H Alkaloids of the Pyridine group could be divided into 4 subgroups and the nucleus of the molecule is one of the N N following nuclei: CH3 Pyridine alone Pyridine with nitrogenous 1. Pyridine alone: e.g. trigonelline rings 2. Pyridone: e.g. ricinine. 3. Pyridine with nitrogenous rings (pyrrole-ring): e.g. tobacco alkaloids 4. Tetrahydropyridine: e.g. Areca alkaloids 5.Piperidine. E.g. pepper , conium, lobelia and pomegranate. Tetrahydropyridine Pyridone In plants, it is the condensation of aspartic acid and glyceraldehydes which leads to nicotinic acid, which is the precursor of other alkaloids of this group such as Areca alkaloids, nicotine, nicotelline, anabasine and ricinine. Nicotine is biosynthesized from nicotinic acid and ornithine or putrescine Piperridine  6-Alkaloids of the Pyridine nucleus Drugs Containing Pyridine Alkaloids 1) Drugs contain Pyridine alone Wood Betony Latin name: Stachys officinalis Family: Labiatae Active constituents: Trigonelline, Stachydrine and Betonine Medicinal use Wood betony was at one time commonly used as a medicinal plant in the treatment of a wide range of disorders, especially as a nervine and tonic for treating maladies of the head and as an external application to wounds. It also stimulates the digestive system and the liver, having an overall tonic effect upon the body.  6-Alkaloids of the Pyridine nucleus Drugs Containing Pyridine Alkaloids 2) Drugs Containing Pyridone Synonym: Ricinus africanus Willd. Family: Euphorbiaceae Constituents ricinine, ergostfucosterol, and probucol components Medicinal Uses ricinine R. communis leaves are tied on the nails affected for the treatment of onychomycosis in District Jacobabad (Sindh). R. communis is anti- abortive, antibacterial, fungicidal, It possessed ant nociceptive and wound healing properties. Extract of R. communis is known for it antioxidant and insecticidal activities.  6-Alkaloids of the Pyridine nucleus Drugs Containing Pyridine Alkaloids H 3) Drugs Containing Pyridine with nitrogenous rings N N Tobacco alkaloids CH3 Nicotiana tabacum (Fam: Solanaceae) The leaves of the tobacco plant are used for production of Cigarettes. They are toxic plants which contain alkaloids. Constituents nicotine plus five minor alkaloids found in tobacco smoke (as nornicotine, the N- oxidized derivatives of nicotine, nicotyrine, anabasine and anatabine.) Nicotine is colorless to pale yellow, very hygroscopic, oily, very strong volatile oil base.  6-Alkaloids of the Pyridine nucleus Drugs Containing Pyridine Alkaloids 3) Drugs Containing Pyridine with nitrogenous rings Tobacco alkaloids Nicotine is colorless to pale yellow, very hygroscopic, oily, very strong volatile oil base. H non-volatile H H liquid N N N H less basic CH3 CH3 N N N H nor-nicotine N (-)-nicotine 2 basic N atoms (major) CH3 N Volatile nicoteine liquids form salts with acids 16  6-Alkaloids of the Pyridine nucleus Drugs Containing Pyridine Alkaloids H 3) Drugs Containing Pyridine with nitrogenous rings N N CH3 tobacco alkaloids Pharmacological actions Nicotine possesses a high affinity to the gangilionic-(nicotinic) cholinergic- receptors. So, it stimulates all autonomic ganglia, it acts Main use: on the CNS causing tremors and conclusions, it is also stimulates the Insecticide & anthelmintic in veterinary respiratory and vomiting centers. It acts on the smooth muscle of the medicine intestine, by increasing tone and motor activity. It acts on the cardiovascular system, by inducing vasoconstriction and  Little use in medicine (high toxicity) an increase in arterial blood pressure. In the long run, nicotine is In small doses (respiratory stimulant) responsible for the genesis of cardiovascular, pulmonary diseases.  In larger doses (respiratory depre) It is used in the form of chewing gum or transdermal system for relieving the symptoms of withdrawal of cigarettes.  Increases incidence of abortion It is also used for treating aphid and other insect infestation.  6-Alkaloids of the Pyridine nucleus Drugs Containing Pyridine Alkaloids 5.Piperidine Piperidine alkaloids are identified by their saturated heterocyclic ring, i.e., piperidine nucleus This group biosynthetically derived from Lysines e.g. alkaloids of: a. Conium. b. Lobelia. c. pepper. d. pomegranate.  6-Alkaloids of the Pyridine nucleus Drugs Containing Pyridine Alkaloids 5.Piperidine a. Conium alkaloids This group occurred in Conium maculatum which has a worldwide distribution; it is a very common plant species, a member of the family Apiaceae (formerly Umbelliferae), This group represent the best known piperidine alkaloid poisons Contents : It contains; coniine , N-methylconiine, conhydrine, seudoconh.drine, Coniine the most important toxic principle of Hemlock, It is found in the seeds of Cicuta maculata L (Water Hemlock). Coniine paralyzes muscles by blocking the nicotinic receptor on the post- synaptic membrane of the neuromuscular junction causing a flaccid paralysis and death  6-Alkaloids of the Pyridine nucleus Drugs Containing Pyridine Alkaloids O N OH CH3 5.Piperidine b. lobelia Occurrence: Its the dried leaves and flowering tops of Lobelia inflate (Fam. Lobeliaceae). Contents: It contains 14 alkaloids (0.2 to 0.5%) including (-)-lobeline, meso-lobelanine and meso-lobelanidine. The chief constituents is (2R, 6S, 8S)(-)-lobeline. Lobeline occurs as colorless crystals that are slightly soluble in water but readily soluble in hot alcohol.  6-Alkaloids of the Pyridine nucleus Drugs Containing Pyridine Alkaloids 5.Piperidine b. lobelia Pharmacology & use: Lobeline produces similar, but weaker, pharmacologic effects to those of nicotine on the peripheral circulation, and the central nervous system. Lobeline is a respiratory stimulant, which enhances and accelerates the respiratory movements by improving the reactivity of the brain stem centers to carbon dioxide. In addition, it is ganglionic stimulant and β-adrenergic bronchodilator. Lobeline sulfate is still commercialized as an adjuvant in smoking cessation program  6-Alkaloids of the Pyridine nucleus Drugs Containing Pyridine Alkaloids 5.Piperidine c. pepper. Black Pepper Black pepper consists of the dried fruit of Piper nigrum (Fam. Piperaceae), a perennial plant originally from the southwest of India and cultivated also in Indonesia, Sri Lanka and South America (Brazil) Constituents : The peppery odor is due to 1 to 3.5% of an essential oil rich in terpenoid hydrocarbons and the pungent taste to Piperidine amides (5- 10%). The chief constituent is piperine (insecticide), an amide of Piperidine and of piperic acid. The other amides are piperidines (piperanine, piperettine) piperolein A and piperolein B, pyrrolidines (piperyline). Uses Peppers are frequently used in Ayurvedic medicine. Piperine is CNS depressant and anticonvulsant in rats. Some of its synthetic derivatives have been used in China as anti-epileptic. Black pepper is used as stomachic.  7-Alkaloids of the Pyridine nucleus 5.Piperidine d- Pomegranate alkaloids. Occurrence: the fruit rind, root bark and stem bark of Punica granatum. The plant is shrub widespread in North (Fam. Punicaceae) Constituents : the bark contains 0.5-0.7% total alkaloids: (-) pelletierine, isopelletierine, and N-methylated analogs. Major alkaloid: pelltierine (liquid). pelletierine tannate (mixture, solid) Pomegranates have astringent properties because of the alkaloids (pelletierine tannate) pelletierine tannate; present in the bark of the stems and roots and have been used for many years as an anthelmintic: removing tapeworms