PHG 322 Pharmacogonsy II lecture 5 Presented by Assistant Prof. Dr. Ebtesam Alsheddi

1. PHG 322Pharmacogonsy IIlecture 5Presented byAssistant Prof. Dr. EbtesamAlsheddi بسم الله الرحمن الرحيم

2. Indole Alkaloids4- RauwolfiaAlkaloids (carbolinealk.) • Source:Rauwolfia roots (Rauwolfiaserpentina, Fam. Apocynaceae) Carboline skeleton

3. Constituents:The most important are Reserpine, Deserpineand Rescinnamine. • Properties: • Reserpine and related alkaloids are weakly basic diester, tertiary alkaloidsand possess a carboxylic group on ring "E".

4. Alkaline Hydrolysis: 1- Reserpine → reserpicacid + trimethoxybenzoic acid + methanol. 2- Recinnamine → reserpicacid + trimethoxycinnamic acid + methanol. • Its solution acquires a yellow color and a pronounced fluorescence especially after the addition of acids or upon exposure to light. • Tests for reserpine: • Vanillin /HCl reagent: → violet color. • Sodium molybdate in H2SO4 → Yellow → Blue in two minutes. • Uses: • Reserpineand the related alkaloidrescinnamineare mainly used as antihypertensives (250-500 mg daily) and as tranquilizers(0.1- 1mg or more daily).

6. Imidazole Alkaloids Pilocarpus Alkaloids • Source: Jaborandi leaves (Pilocarpus jaborandi). • Constituents: (+)-Pilocarpine. • Properties: 1- Oily liquid miscible with water. 2- Non-volatile liquid alkaloid. 3- Lactone function. • Test: Helche’s test: Alkaloid + Dil acid + K2CrO7 → violet colour (Pilocarpine dichromate) • Uses: 1- Miotic. 2- Diaphoretic. 3- Hair preparations.

8. Characters 1. Pilocarpine is oily non-volatile liquid alkaloid. Effects/Uses: • Pilocarpine is a cholinergic agent causing constriction of the pupil (Antagonistic to Atropine). • Pilocarpinesalts are valuable in ophthalmic practice and are used in eye drops as miotics and for the treatment of glaucoma. • Pilocarpine gives relief for dryness of the mouth that results in patients undergoing radiotherapy for mouth and throat cancers.

9. Tropolone Alkaloids Colchicum Alkaloids • Source: Colchicum Corm. • Constituents: Colchicine. • Properties: 1- Neutral Alkaloid. 2- Amid function. • Test: 1- Red colour with FeCl3. 2- Yellow colour with dil. Mineral acids. • Uses: 1- Treatment of Gout. 2- Anticancer in vitro. 3- Treatment of Mediterranean Sea fever. 4- Polyploidy in Plants.

11. Alkaloids with Exocyclic Nitrogen(Protoalkaloids- Phenylalkylamines- Biological amines) • This group of alkaloids have the nitrogenatomlocated in an amino group and is not a member of a heterocyclic ring • Many are simple derivatives of Phenylethylamineand as such, are derived from the common amino acids Phenylalanine or Tyrosine. phenylalanine tyrosine • They are sympathomimetic drugs (e.g. rise the blood pressure).

12. Protoalkaloids includes the alkaloids of: Ephedra alkaloids Khat alkaloids Peyotealkaloids

13. Alkaloids with Exocyclic Nitrogen(Protoalkaloids- Phenylalkylamines- Biological amines) especially Ephedrasinica(Family Ephedraceae). * 1- Ephedra Alkaloids Source: Ephedra Herb (Ma Huang, Yellow Hemp). Ephedra used as remedy for Asthma in Chinese medicine. (-)-Ephedrine is the major Alkaloid in Ephedra. Ephedrine is a phenylalkylamine with N atom in the side chaine

15. Ephedrine is similar to adrenaline in structures. • Advantages of Ephedrine over adrenaline: 1- Orally active. 2- Prolonged action Adrenaline is used to treat a number of conditions including: cardiac arrest, anaphylaxis, and superficial bleeding.It has been used historically for bronchospasm and hypoglycemia, but newer treatments for these, such as salbutamol, a synthetic epinephrine derivative, and dextrose, respectively, are currently preferred.[8]

16. Effects/Uses of Ephedrine • Its pharmacological action resembles epinephrine (adrenaline), but is considerably less active. • Ephedrine can be absorbed orally, unlike epinephrine. • Ephedrine increases blood pressure and heart rate. • It is a potent nasal decongestant due to its vasoconstrictor action on blood capillaries of mucous membranes. • Ephedrine has a longer duration of action.

17. Chen’stest: Ephedrine HCl in water + 0.1 ml CuSO4 + 1ml NaOH → Violetcolour, shake with Ether→ Ether layer → purple Aqueous layer → blue

18. 2- Cathe Alkaloids (Kat القات) Khat or “ Abyssinian tea” consists of the fresh leaves of Catha Edulis (Family Celastraceae). • CNS stimulant activity • Abused drug.

19. 3- Peyote Alkaloids • Source: Lophophorawilliamsii( is a small, spineless cactus) • Hallucinogenic • Major alkaloid

20. Purines are derivatives of a heterocyclic nucleus consisting of a six-membered Pyrimidine ring fused to a five-membered Imidazole ring. Purines are Psudoalkaloids (Are not derived from amino acids but have nitrogen in a heterocyclic ring) (True alkaloid- protoalkaloid- pseudoalkaloid)

21. They are all methyl derivatives of xanthine.

22. Chemical test: • Do not give precipitate with Mayer's reagent. • They give a positive Murexide test (special test). * are weak basesform salts only with strong acids

23. Caffeine: • Is the best CNS stimulant of the purine bases and has weak diuretic action. Source: Coffee seeds – Sеmina CoffeaeArabian coffee tree --CoffeaarabicaFam.–Rubiaceae Added to the analgesics

24. Theobromine: • Has little CNS stimulant action, but has more diuretic activity, and has smooth muscle relaxant effect. From Theobroma cacao tree

25. 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. Tea Leaves – Folia TheaeChinese Tea – TheasinensisFamilyTeas – Theaceae

26. Marine Bioactive Agent

27. Over 70% of the earth's surface is covered by oceans which contain 95% of the earth's biosphere • Marine environments are considered more biologically diverse than terrestrial environments • Ocean contain highly ecological, chemical & biological diversity starting from micro-organisms to vertebrates. This diversity has been the source of unique chemical compounds, which hold tremendous pharmaceutical potential.

28. Marine Bioactive Agent, Marine bioactive compounds or Marine natural products (MNPs) are organic compounds produced by microbes, sponges, seaweeds, and other marine organisms. The host organism synthesizes these compounds as secondary metabolites to protect themselves and to maintain homeostasis in their environment.

29. Marine organisms are able to generate bioactive compounds to protect themselves from external factors. • Recently, scientists have explored various health beneficial pharmaceutical bioactives from marine bio resources such as macroalgea, microalgea, fungi, bacteria, actinomycetes, invertebrates and vertebrates.

30. The number of potential compounds isolated from marine exceeds to 10000 • with hundred of new compounds still being discovered every year • A number of promising identified molecules are already in market, clinical trials or preclinical trials