PHG 322 Pharmacogonsy II lecture 1 Presented by Assistant Prof. Dr. Ebtesam Alsheddi

1. PHG 322Pharmacogonsy IIlecture 1Presented byAssistant Prof. Dr. EbtesamAlsheddi بسم الله الرحمن الرحيم

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

3. 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

4. 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

5. 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

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

7. Important Book/Thesis:

8. The assessment tasks during the semester:

9. 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.

10. 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

11. 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

12. Nomenclature • Alkaloids terminate with the suffix: (ine) • Their names may be derived from: • Genusname e.g. Atropine from Atropa • Speciesname e.g. Cocaine from Coca • Commonname e.g. Ergotamine from Ergot • Physiologicalactivity e.g. Emetine (emetic) • Discoverere.g. Pelletierine from Pelletier

13. Prefixes and suffixes These are, usually,addedto the name of theparentalkaloid and are used to designaterelatedalkaloids, generally present in thesameplant. Examples are: I. Prefixes • Nor-: designatesN-demethylation or N-demethoxylatione.g.Nornicotine • Apo-: designatesdehydratione.g. Apomorphine • Iso-,Pseudo-,Neo-andEpi-indicate different types of isomers

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

15. Most alkaloids colourless -colchicine & berberineyellow - canadineorange Physical properties: 1) Condition: • Most alkaloids arecrystalline solids • Some are liquids non-volatile volatile e.g. pilocarpine and hyoscine e.g. nicotine and coniine 2) Colour: • Some are coloured:

16. 3) Solubility: • Solubility of alkaloids & their salts is importantbecause: a) They are often administered in solution b) Differencesin solubility between alkaloids& their saltsis used for: - isolation of alkaloids -purificationfromnon-alkaloidalsubstances

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

18. 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-ephedrineis 3.5 times more active than d-ephedrine. • l-ergotamineis 3-4 times more active than d-ergotamine. • d- Tubocurarineis 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.

19. nicotine coniine Chemical properties: • Alkaloids contain:C, H, N • Most of them contain oxygen • Fewalkaloids are oxygen free

20. Chemical Properties: 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.gd-Tubocurarine II- Basicity: • R2-NH > R-NH2 > R3-N • Saturated hexacyclic amines is more basic than aromatic amines.

21. 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

22. 2) Type of amino group: • N in alkaloids → in form of amine Primaryamino group Secondaryamino group Tertiaryamino group Quaternaryammonium ion e.g. Norpseudo-ephedrine Ephedrine Nicotine Tubocurarine

23. ] [ Alkaloid [ ] 3) Basicity: • A lone pair of electronsonN atom→ basic character →alkaloidsresembleNH3in chemical characters →formsaltswithacidswithout liberation of H2O +H+Cl- Alkaloid hydrochloride 23 Present as:

24. Pyridine Piperidine increase basicity decrease basicity unsaturationdecreases basicity 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 Electron releasing groups Electron withdrawing gps e.g. carbonyl group e.g. alkyl group Piperidinealkaloids → morebasicthanpyridinealkaloids

25. Narceine → Alkaloids may be: • Neutral (not basic) Ricinine →electronavailabilityon nitrogen atomdecreases • Amphoteric →due to the presence of acidic group(s) e.g. phenolicalkaloids e.g.alkaloids containing carboxylic group Morphine