PHG 322PHARMACOGONSY IILECTURE 5PRESENTED BYASSISTANT PROF. DR. EBTESAM ALSHEDDI

الرحيم الرحمن الله بسم

• Source: Rauwolfia roots (Rauwolfia serpentina, Fam. Apocynaceae)

Indole Alkaloids4- Rauwolfia Alkaloids (carboline alk.)

Carboline skeleton

• Constituents: The most important are Reserpine, Deserpine and Rescinnamine.

• Properties: Reserpine and related alkaloids are weakly basic diester,

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

NH

NH3CO

H3COOC OR

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

E

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 H2SO4 → 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.

• Test:Helche’s test: Alkaloid + Dil acid + K2CrO7 → violet colour

(Pilocarpine dichromate)• Uses:

1- Miotic. 2- Diaphoretic.3- Hair preparations.

N

N O

CH3

O

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.

Effects/Uses:

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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.

H3CO

H3CO

OCH3

OCH3

O

NH-CO-CH3

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.

CH2 C

H

NH2

COOHOH

phenylalanine tyrosine

CH2 C

H

NH2

COOH

They are sympathomimetic drugs (e.g. rise the blood

pressure).

1) Ephedra alkaloids

2) Khat alkaloids

3) Peyote alkaloids

Protoalkaloids includes the alkaloids of:

Alkaloids with Exocyclic Nitrogen(Protoalkaloids- Phenylalkylamines- Biological amines)

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

especially Ephedra sinica (Family Ephedraceae). *

• 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 CuSO4 + 1ml NaOH → Violet

colour, shake with Ether →

Ether layer → purpleAqueous layer → blue

2- Cathe Alkaloids (Kat القات)Khat or “ Abyssinian tea” consists of

the fresh leaves of Catha Edulis

(Family Celastraceae).

CNS stimulant activity Abused drug.

CH CH CH3

NH2

OH

Cathine

C CH CH3

NH2

O

Cathinone

3- Peyote Alkaloids

NH2

H3CO

H3CO

OCH3

Mescaline

• Source: Lophophora williamsii ( is a small, spineless cactus)

• Hallucinogenic • Major alkaloid

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)

Purine alkaloids

xanthine

theophyillinecoffeine theobromine

Purine alkaloids

They are all methyl derivatives of xanthine.

* are weak bases form salts only with strong acids

Do not give precipitate with Mayer's reagent. They give a positive Murexide test (special test).

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Chemical test:

Caffeine:

Is the best CNS stimulant of the purine bases and has weak

diuretic action.

Source: Coffee seeds – Sеmina CoffeaeArabian coffee tree --Coffea arabicaFam. – 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 TheaeChinese Tea – Thea sinensisFamily 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