ميحرلا نمحرلا الله مسب

PHG 322 PHARMACOGONSY II LECTURE 5

PRESENTED BY ASSISTANT PROF. DR. EBTESAM ALSHEDDI

Indole Alkaloids

4 - Rauwolfia Alkaloids (carboline alk.) •

Source:

Rauwolfia roots (Rauwolfia

serpentina, Fam. Apocynaceae)

Carboline skeleton

•  •

Constituents:

Rescinnamine.

The most important are Reserpine, Deserpine and

Properties:

Reserpine and related alkaloids are weakly basic diester,

tertiary alkaloids and possess a carboxylic group on ring "E".

N H 3 CO N H

E

H 3 COOC OR

R= 3,4,5-trimethoxybenzoic acid Reserpine R= 3,4,5-trimethoxycinnamic acid Recinnamine



Alkaline Hydrolysis:

1- Reserpine → reserpic acid + trimethoxybenzoic acid + methanol. 2- Recinnamine → reserpic acid + 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 H 2 SO 4 → Yellow → Blue in two minutes.

• 

Uses: Reserpine and the related alkaloid rescinnamine are mainly used as antihypertensives (250-500 mg daily) and as tranquilizers (0.1- 1mg or more daily).

• • • • •

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.

N N

Test: Helche’s test: Alkaloid + Dil acid + K 2 CrO 7 → violet colour (Pilocarpine dichromate) Uses: 1- Miotic.

3- Hair preparations.

2- Diaphoretic.

CH 3 O O

8 Effects/Uses:



Pilocarpine is a cholinergic agent causing constriction of the pupil ( Antagonistic to Atropine).



Pilocarpine salts 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.

Tropolone Alkaloids

• • • • •

Colchicum Alkaloids Source: Colchicum Corm.

Constituents: Colchicine.

Properties: 1- Neutral Alkaloid.

H 3 CO H 3 CO

2- Amid function.

Test: 1- Red colour with FeCl 3 .

2- Yellow colour with dil. Mineral acids.

OCH 3

Uses: 1- Treatment of Gout.

2- Anticancer in vitro.

3- Treatment of Mediterranean Sea fever.

4- Polyploidy in Plants.

NH-CO-CH 3 OCH 3 O

 

Alkaloids with Exocyclic Nitrogen (Protoalkaloids- Phenylalkylamines- Biological amines) This group of alkaloids have the nitrogen atom located in an amino group and is not a member of a heterocyclic ring Many are simple derivatives of Phenylethylamine and as such, are derived from the common amino acids Phenylalanine or Tyrosine .



H CH 2 C NH 2 COOH phenylalanine H O H CH 2 C NH 2 COOH tyrosine They are sympathomimetic drugs (e.g. rise the blood pressure).

Protoalkaloids includes the alkaloids of:

1)

Ephedra alkaloids 2) Khat alkaloids 3) Peyote alkaloids

Alkaloids with Exocyclic Nitrogen

(Protoalkaloids- Phenylalkylamines- Biological amines) 1- Ephedra Alkaloids



Source: Ephedra Herb (Ma Huang, Yellow Hemp).



especially Ephedra sinica (Family Ephedraceae). * 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

• • 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]

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 .

Chen’s test:

Ephedrine HCl in water + 0.1 ml CuSO 4 colour, shake with Ether → + 1ml NaOH → Violet Ether layer → purple Aqueous layer → blue

2- Cathe Alkaloids (Kat تاقلا )

Khat or “ Abyssinian tea” consists of the fresh leaves of Catha Edulis (Family Celastraceae).

 CNS stimulant activity  Abused drug.

OH CH CH NH 2 CH 3 O C CH NH 2 CH 3

Cathine Cathinone

3- Peyote Alkaloids

• • • Source: Lophophora williamsii ( is a small, spineless cactus) Hallucinogenic Major alkaloid H 3 CO H 3 CO OCH 3 NH 2

Mescaline

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)

coffeine

Purine alkaloids

xanthine theobromine theophyilline



They are all methyl derivatives of xanthine.

Chemical test:



Do not give precipitate with Mayer's reagent .



They give a positive Murexide test (special test).

* are weak bases form salts only with strong acids 22



Caffeine: Is the best CNS stimulant of the purine bases and has weak diuretic action.

Source: Coffee seeds

– S е mina Coffeae

Arabian coffee tree --

Coffea arabica

Fam.

– Rubiaceae Added to the analgesics



Theobromine: Has little CNS stimulant action, but has more diuretic activity, and has smooth muscle relaxant effect.

From Theobroma cacao tree



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 Theae

Chinese Tea

– Thea sinensis

Family Teas – Theaceae

Marine Bioactive Agent

• • • • 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.

• • 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.

• • 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.

• • • 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