Isoquinoline and Quinoline Alkaloids PDF, PHA 3, 1/7/2021

QUINOLINE AND ISOQUINOLINE ALKALOIDS PHA III Florence Nalimu, Pharmacy and Pharmaceutical Sciences 1 QUINOLINE ALKALOIDS 2 Biosynthetic origin Quinoline alkaloids are derived from anthranilic acid. Florence Nalimu, Pharmacy and Pharmaceuti...

QUINOLINE AND ISOQUINOLINE ALKALOIDS PHA III Florence Nalimu, Pharmacy and Pharmaceutical Sciences 1 QUINOLINE ALKALOIDS 2 Biosynthetic origin Quinoline alkaloids are derived from anthranilic acid. Florence Nalimu, Pharmacy and Pharmaceutical Sciences 3  Distribution They mainly occur in Rutaceous plants. They are also found in the families Annonaceae and Moraceae Florence Nalimu, Pharmacy and Pharmaceutical Sciences 4  Cinchona spp It belongs to Rubiaceae family. The bark is a rich source of active compounds including quinine, quinidine, cinchonine, and cinchonidine Florence Nalimu, Pharmacy and Pharmaceutical Sciences 5  It contains steroisomers of alkaloids. Quinine (–), Quinidine (+) and cinchonine (+) and Cinchonidine (–) other alkaloids are present & anthraquinones. Alkaloids are present in the parenchyma cell of the bark in combination with quinic acid and cinchotannic acid (Phlobatannins, phlobaphenes) red colour. Florence Nalimu, Pharmacy and Pharmaceutical Sciences 6  5 1/7/2021 Florence 1/7/2021 Nalimu, Pharmacy and Pharmaceutical Sciences 1/7/2021 77 7 Uses Quinine has antipyretic, antimalarial, analgesic and anti-inflammatory properties and a bitter taste. Quinidine for cardiac arrhythmias Florence Nalimu, Pharmacy and Pharmaceutical Sciences 8  The quinoline nucleus is now of interest in the development of anticancer compounds Florence Nalimu, Pharmacy and Pharmaceutical Sciences 9 ISOQUINOLINE ALKALOIDS 10 Biosynthetic origin Isoquinoline alkaloids are derived from tyrosine Florence Nalimu, Pharmacy and Pharmaceutical Sciences 11 Distribution Isoquinoline alkaloids are widely distributed among plants coming from the families Papaveraceae (where they are mostly present in the form of tetrahydro-bases), Berberidaceae, Fumariaceae, Menispermaceae, Ranunculaceae, Rutaceae, and Annonaceae Florence Nalimu, Pharmacy and Pharmaceutical Sciences 12  Cephaelis ipecacuanha It is commonly known as ipecacuanha (ipecac). It belongs to family Rubiaceae. The alkaloids are present in the roots of the plant. It is commonly used in cases of suspected poisoning. Main actives: emetine, cephalein and psychotrine Ipecac works by producing irritation on the gastric mucosa hence causing vomiting. Florence Nalimu, Pharmacy and Pharmaceutical Sciences 13  Uses: given by mouth cases of suspected poisoning. Also used in cases of severe amoebic dysentery. Used as an expectorant. Contraindicated in digestive disorders like ulcers or Crohn’s disease. Large doses of emetine can damage the heart, liver, kidneys, intestinal tract, and skeletal muscle. Misuse of ipecacuanha by patients with anorexia nervosa and bulimia has resulted in severe myopathy, lethargy, erythema, dysphagia, cardiotoxicity, and even death. Florence Nalimu, Pharmacy and Pharmaceutical Sciences 14 Chondodendron tomentosum The stems of this plant are a source of ‘curare’ (d- tubocurarine). It belongs to family Menispermaceae Tubocurarine is an alkaloid of the benzylisoquinoline type. Tubocurarine is a quaternary ammonium compound soluble in water and alcohol, insoluble in CHCl3, acetone and ether. Florence Nalimu, Pharmacy and Pharmaceutical Sciences 15  It is competitive antagonist at cholinergic nicotinic receptors at the neuromuscular junction. Tubocurarine is relatively contra indicated in asthmatic patients and in those with an allergic tendency. Has been replaced by safer skeletal muscle relaxants like rocuronium, vecuronium and atracurium Florence Nalimu, Pharmacy and Pharmaceutical Sciences 16 Papaver somniferum It is commonly known as opium poppy and belongs to family Papaveraceae. Opium is the air dried milky exudate obtained by incision from the unripe capsules of the plant Florence Nalimu, Pharmacy and Pharmaceutical Sciences 17  Contain phenanthrene Morphine nucleus, they are strong bases, Codeine alkaline to litmus and highly Thebaine toxic i.e with more CNS depressant activity. 4 1/7/2021 Florence 1/7/2021 Nalimu, Pharmacy and Pharmaceutical Sciences 1/7/2021 5 18 18  Noscapine contain benzyl–isoquinoline, (Narcotine) they are weak bases, slightly Narceine toxic with more antispasmodic Papaverine activity. 4 1/7/2021 Florence 1/7/2021 Nalimu, Pharmacy and Pharmaceutical Sciences 1/7/2021 5 19 19  Codeine Morphine Thebaine Heroin (synthetic) Noscapine Narceine Papaverine Naloxone: It is narcotic anagonist with no analgesic effect, for heroin addiction, competes with narcotics for the sites on narcotic receptors. INDOLE ALKALOIDS 23  INDOLE ALKALOIDS Indole alkaloids are a class of alkaloids containing a structural moiety of indole; many indole alkaloids also include isoprene groups and are thus called terpene indole or secologanin tryptamine alkaloids Florence Nalimu, Pharmacy and Pharmaceutical Sciences 24  Distribution They are widely distributed in flowering plants. They are also found in fungi(ergot ) as well as in several species of the Convolvulaceae family Florence Nalimu, Pharmacy and Pharmaceutical Sciences 25  Physostigma venenosum Calabar beans are dried ripe seeds of Physostigma venenosum (Leguminosae), west Africa. The major active is physostigmine eserine is present to extent of 0.15 – 0.3%. Florence Nalimu, Pharmacy and Pharmaceutical Sciences 26 Vinca alkaloids (Vinblastine) VLB. Vincristine,(Leurocristine) LC. Obtained from (Periwnkle plant) Catharanthus roseus (Vinca rosea) of the family Apocynaceae, about 90 alkaloids have been isolated from C. roseus Florence Nalimu, Pharmacy and Pharmaceutical Sciences 27 Florence Nalimu, Pharmacy and Pharmaceutical Sciences 28  ERGOT ALKALOIDS (ergot- ‘spur’) Ergot: Is the dried sclerotium of the fungus Claviceps purpurea (Clavicipitaceae), arising in the ovary of the Rye (Europe). Florence Nalimu, Pharmacy and Pharmaceutical Sciences 29  In the Middle Ages, humans suffering from a disease called St. Anthony's fire reportedly experienced symptoms that suggested ergot poisoning such as burning skin, insects crawling under their skin, and the loss of hands and feet (gangrene), CNS effects and GIT effects. Six pairs of alkaloids are known in three groups: 1. water soluble: Ergometrine or (Ergonovine). 2. water insoluble: Ergotamine. 3. water insoluble: Ergotoxine groups. All are combined with lysergic acid or isolysergic acid which gives rise to the physiologically active alkaloids. 5 1/7/2021 Florence 1/7/2021 Nalimu, Pharmacy and Pharmaceutical Sciences 1/7/2021 30 30  Table 1. Alkaloids of the ergot sclerotium Group Alkaloid Formula Discovered Ergometrine Dudley & Moir 1.Ergometrine C19H22O2N3 Ergometrinine (1935) group Ergotamine Spiro & Stoll C33H35O5N5 Ergotaminine (1920) 2.Ergotamine Ergosine Smith & Timmis C30H37O5N5 group Ergosinine (1937) Ergocristine Stoll & C35H39O5N5 Burckhardt Ergocristinine (1937) Ergocryptine 3.Ergotoxine C32H41O5N5 group Ergocryptinine Stoll & Hofmann Ergocornine (1938,1943) C31H39O5N5 Ergocorninine 5 1/7/2021 Florence 1/7/2021 Nalimu, Pharmacy and Pharmaceutical Sciences 1/7/2021 31 31 31  Ergometrinine Ergometrine (uterine contractions) Ergotamine (migrane headache)  Although all natural ergot alkaloids have qualitatively the same effect on the uterus, ergonovine is most active and also less toxic hence its now preferred in obstetrics. Its semi-synthetic derivative methylergonovine is also used. Although ergot derivatives have been superseded in the treatment of migraine by drugs such as sumatriptan, their influence means their place in history is assured. Ergot derivatives are also used in the treatment of Parkinson’s disease as dopamine agonists Florence Nalimu, Pharmacy and Pharmaceutical Sciences 33 Assignment Describe the identification tests for the different classes of alkaloids. Outline the physical and chemical properties of the Quinoline and isoquinoline alkaloids Outline the doses used when ipecac is used locally in treatment of different conditions. Write short notes on Rauwolfia serpentina. Florence Nalimu, Pharmacy and Pharmaceutical Sciences 34  Thanks Florence 07/01/2021 Nalimu, Pharmacy and Pharmaceutical Sciences 35 35