بسم الله الرحمن الرحيم PHG 322 Pharmacogonsy II lecture 1 Presented by Assistant Prof. Dr. Ebtesam Alsheddi

Office: second flour # 84 Email: ebtesam.saad@yahoo.com Site: faculty.ksu.edu.sa/10252

Topics to be covered: (cont.) 1) Plants containing Alkaloids (botanical and chemical characters): Introduction Phenylalkylamine, Tropolone and Imidazole alkaloids Pyridine and piperidine alkaloids Tropane alkaloids Quinoline and isoquinoline alkaloids Opium alkaloids Indole alkaloids Carboline, purine, steroidal and terpenoidal alkaloids

Topics to be covered: 2) Marine derived drugs: Biomedical potential of marine natural products Microalgae as a drug source Biologically active substances from marine sponges

Topics to be covered: 3) Plants containing Glycosides (botanical and chemical characters): Introduction Phenolic, cyanogenic and thioglycosides Coumarins, flavonoidal glycosides and related compounds Anthracene derivatives Cardiac glycosides Saponins

Topics to be covered: 4) Toxicological Pharmacognosy: Poisonous plants Plants as drugs of abuse Hepatotoxic plants Toxic mushrooms 3) Herb-drug interactions

Important Book/Thesis: No. Book/Thesis Editor or Author Date of pub. Name of Publisher 1 Pharmacognosy 16th edition Trease and Evans 2009 Saunders London, New York, … 2 النباتات السامة في المملكة العربية السعودية عبد الله بن أحمد الأمير 2000 جامعة الملك سعود كلية العلوم قسم النبات والأحياء الدقيقة 3 Bioactive Marine Natural Products Bhakuni and Rawat 2005 Anamaya Publishers, New Delhi, India

First ½ of semester (Exam + Activity/Quiz) The assessment tasks during the semester: Marks Assessment task Dr. Rababb Dr. Ebtesam - 18 First ½ of semester (Exam + Activity/Quiz) Second ½ of semester 24 Practical 20 Final Exam 100 Total

Deviation from Definition Alkaloids Definition Alkaloids, which mean alkali-like substances, are basic nitrogenous compounds of plant or animal origin and generally possessing a marked physiological action on man or animals. The nitrogen is usually contained in a heterocyclic ring system. Deviation from Definition Some alkaloids are not basic e.g. Colchicine, Piperine, Few alkaloids contain nitrogen in a non-ring system e.g. Ephedrine, Colchicine. Mescaline 3) Plant origin: Some alkaloids are derived from bacteria, fungi, insects, frogs, animals.

Function of alkaloids in plants 1) Protective function against insects or herbivores 2) They are end products (detoxification) 3) Source for energy and reserve of nitrogen

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

Nomenclature Alkaloids terminate with the suffix: (ine) Their names may be derived from: Genus name e.g. Atropine from Atropa Species name e.g. Cocaine from Coca Common name e.g. Ergotamine from Ergot Physiological activity e.g. Emetine (emetic) Discoverer e.g. Pelletierine from Pelletier

Prefixes and suffixes I. Prefixes These are, usually, added to the name of the parent alkaloid and are used to designate related alkaloids, generally present in the same plant. Examples are: I. Prefixes Nor-: designates N-demethylation or N-demethoxylation e.g. Nornicotine Apo-: designates dehydration e.g. Apomorphine Iso-, Pseudo-, Neo- and Epi- indicate different types of isomers

II. Suffixes 1) –dine: designates isomerism as in case of the Cinchona alkaloids quinine (l) & quinidine (d) cinchonidine (l) & cinchonine (d) 2) –ine: indicates, in case of ergot alkaloids, a lower pharmacological activity e.g. ergotaminine is less potent than ergotamine

Physical properties: Most alkaloids are crystalline solids 1) Condition: Most alkaloids are crystalline solids Some are liquids volatile non-volatile e.g. nicotine and coniine e.g. pilocarpine and hyoscine 2) Colour: Most alkaloids colourless Some are coloured: - colchicine & berberine yellow - canadine orange

Solubility of alkaloids & their salts is important because: a) They are often administered in solution b) Differences in solubility between alkaloids & their salts is used for: - isolation of alkaloids - purification from non-alkaloidal substances

- lobeline hydrochloride → CHCl3 (soluble) Solvent Alkaloidal bases Alkaloidal salts Alcohol Soluble Soluble Soluble except: Insoluble except: Organic solvents - morphine & psychotrine → insol. in ether - lobeline hydrochloride → CHCl3 (soluble) - theobromine & theophylline → benzene (insol.) Insoluble except: H2O Soluble except: quinine sulphate → insoluble in H2O - caffeine - ephedrine - codeine - colchicine - pilocarpine - quat. ammonium bases

Optically active isomers may show different physiological activities. 4) Optical activity: Many alkaloids are optically active due to ? → presence of one or more asymmetric carbon atom(s) 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.

Chemical properties: Alkaloids contain: C, H, N Most of them contain oxygen Few alkaloids are oxygen free nicotine coniine

Chemical Properties: Primary amines R-NH2 e.g. Norephedrine I- Nitrogen: Primary amines R-NH2 e.g. Norephedrine Secondary amines R2-NH e.g. Ephedrine Tertiary amines R3-N e.g. Atropine Quaternary ammonium salts R4-N e.g d-Tubocurarine II- Basicity: R2-NH > R-NH2 > R3-N Saturated hexacyclic amines is more basic than aromatic amines.

1) Nitrogen in alkaloids Basicity Number of nitrogen atoms Type of amino group 1) Number of nitrogen atoms: Usually one N atom Some contain more than one → up to 5 N atoms e.g. nicotine → two ergotamine → five 21

Quaternary ammonium ion 2) Type of amino group: N in alkaloids → in form of amine Primary amino group Secondary amino group Tertiary amino group Quaternary ammonium ion e.g. Norpseudo-ephedrine Ephedrine Nicotine Tubocurarine

3) Basicity: A lone pair of electrons on N atom → basic character → alkaloids resemble NH3 in chemical characters → form salts with acids without liberation of H2O ] [ Alkaloid + H+Cl- Alkaloid hydrochloride 23 ] [ Present as:

Factors influencing the degree of basicity: Structure of the molecule Presence & position of other substituents & fuctional groups e.g. degree of unsaturation of heterocyclic ring Pyridine Piperidine Electron withdrawing gps Electron releasing groups e.g. carbonyl group e.g. alkyl group Piperidine alkaloids → more basic than pyridine alkaloids increase basicity decrease basicity unsaturation decreases basicity

→ Alkaloids may be: Neutral (not basic) Ricinine → electron availability on nitrogen atom decreases Amphoteric → due to the presence of acidic group(s) e.g. alkaloids containing carboxylic group e.g. phenolic alkaloids Narceine Morphine