Chemical nature of natural drugs

Chemical Nature of Natural Drugs

Dr. Yogesh V. UshirM. Pharm, PhD,

SMBT Institute of D. Pharmacy, Dhamangaon

Plant Metabolism

Primary Metabolism:

Biochemistry Processes resulting in primary metabolites (carbohydrate, amino acid,..)

Secondary Metabolism:

Natural Products chemistry resulting in secondary metabolites (alkalaoids, terpenoids…). Building blocks for 2ry metabolites are derived from 1ry metabolites.

Secondary Metabolism

Secondary Metabolites are the end products obtain in Secondary Metabolism are;Alkaloids GlycosidesTerpenoids Volatile oilsTanninsResins

Alkaloids

Are the alkali like substances, which are complex in nature consist nitrogen in there structure.

Occurrence

Naturally occurring compounds in plants (mainly!)

Also found in Fungi, Bacteria, Marine

Extracted from seeds, fruits, leave, roots and barks

Occurring in the form of salt with organic acids

Common precursors are amino acids

Rare in lower plants. Dicots are more rich in alkaloids than

Monocots. Families rich in Alkaloids: Apocynaceae,

Rubiaceae, Solanaceae and Papaveracea.

Families free from Alkaloids: Rosaceae, Labiatae

Distribution

Distribution in plants

All Parts e.g. Datura.Barks e.g. CinchonaSeeds e.g. Nux vomicaRoots e.g. AconiteFruits e.g. Black pepperLeaves e.g. TobaccoLatex e.g. Opium

Properties

Bitter tasting, generally white solids (exception - nicotine is a brown liquid).

Sparingly soluble in water. But alkaloidal salts are freely soluble in water.

Free alkaloids are soluble in ether, chloroform and non-polar solvent.

Many have heterocyclic rings as a part of their structure Many are basic (“alkaline”, due to an unshared pair on N) Optically active isomers of alkaloids may show different

physiological activities. Alkaloids are decomposed by heat, except Strychnine and caffeine

Forms of Alkaloids

Free bases Salts with Organic acids e.g. Oxalic, acetic

acids Salts with inorganic acids e.g. HCl, H2SO4. Salts with special acids: e.g. Meconic acid in Opium

Quinic acid in Cinchona Glycosidal form e.g. Solanine in Solanum.

Function in Plants They may act as protective against insects and

herbivores due to their bitterness and toxicity. They are, in certain cases, the final products of

detoxification (waste products). Source of nitrogen in case of nitrogen deficiency. They, sometimes, act as growth regulators in

certain metabolic systems. They may be utilized as a source of energy in

case of deficiency in carbon dioxide assimilation.

Nomenclature:Names should end by "ine". These names may refer to: The genus of the plant, such as Atropine from Atropa

belladona. The plant species, such as Cocaine from Erythroxylon

coca. The common name of the drug, such as Ergotamine from

ergot. The name of the discoverer, such as Pelletierine that was

discovered by Pelletier. The physiological action, such as Emetine that acts as

emetic, Morphine acts as narcotic. A prominent physical character, such as Hygrine that is

hygroscopic.

Extraction, purification andIsolation of Alkaloids

Method I The powder is treated with alkalis to liberates the free bases

that can then be extracted with water immiscible organic solvents.

Method II The powdered material is extracted with water or aqueous

alcohol containing dilute acid. Alkaloids are extracted as their salts together with accompanying soluble impurities.

Method III The powder is extracted with water soluble organic solvents

such as MeOH or EtOH which are good solvents for both salts and free bases.

Plant material and solvent

Extract

Concentration

Acidified Extract (Alk. as salts)

Organic solvent dissove Impurities

Acidification

Alkalinization

Alkaline aqueous layer

Organic solvent dissove Alkaloids

Identifications tests

Wagner's test: (I2/kI):Reddish brown precipitate .

Mayer’s: (HgCl2) Creamy precipitate with True alkaloid.

Hagger's test: (Picric acid) Yellow precipitate with True alkaloid.

Dragendroff: (Potassium Bismuth Iodide) Reddish Brown precipitate .

Tannic acid solution: different alkaloid colored precipitate .

Classification

Class or Type Examples Tropane Atropine (Datura)

Indole Vinblastin (Viinca), Reserpin (Rauwolfia)

Steroids Connesine (Kurchi)

Purine Caffeine (Coffee), Theophylline (Tea)

Quinoline Quinine (Cinchona)

Isoquinoline Emetine (Ipecac), morphine (Opium)

Pyridine & piperidine Nicotine (Tobacco), Arecholine (Areca nut)

Imidazole Pilocarpine (pterocarpus)

Quinazoline Vasicine (Vasaka)

Amino alkaloids Ephedrine (Ephedra)

Therapeutic effects and pharmaceutical application

Depends on chemical type of alkaloid so vary in effects and uses;

Example of alkaloid Effects/Uses/Application Reserpine Antihypertensive

Caffeine, theophylline, theobromine CNS stimulant

Emetine Vommitting inducer

Vasicine, codeine Anticough agent, expectorant

Morphine CNS depressant

Quinine Antimalerial

Vinblastine, vincristine, taxol Anticancer

Glycosides

Glycosides are non-reducing organic compounds that on hydrolysis with acids, alkalis or enzymes yield;

A sugar part (or glycone, formed of one or more sugar units) and A non-sugar part (or aglycone, also called genin).

Occurrence

occur in higher plant tissues in very small amounts

also in fungal and bacterial cells and animals

Distribution in plants

All Parts e.g. Purple grapesBarks e.g. Wild cherry Seeds e.g. Linseed, Ammi Roots e.g. LiquoriceFruits e.g. Reetha, OrangeLeaves e.g. Senna, Aloe

Properties

Colorless, crystalline, non-reducing compound Non volatile Usually bitter in taste Optically active compounds They are semi-polar in nature Soluble in ethanol and methanol Hydrolyzed by acid, alkali and enzymes After hydrolysis they give sugar (glucose/

mannose/rhamnnose etc) and non-sugar moiety Because of sugar or glycone moiety it gives Molish’s test

positive

Extraction, purification andIsolation of glycosides

Polar substances – soluble in polar solvents

Extraction: starting material should be well dried and carefully

stored enzymes will decompose glycosides if >10% water content

remaining cold extraction procedure (room temp)

with percolation and maceration water, water/alcohol mixture or alcohol

depending on mol wt

Purification: solvent/solvent partition

H2O/hexane or CH3Cl to remove pigments in the non-polar phase

or adsorption methods make column and do chromatography or mix with adsorbants (Celite, Fuller’s Earth, graphite) or use heavy metal to precipitate out impurities

should end up with clear (or coloured) alcoholic extract

crystallisation – final stage

Classification

Class or Type Examples Phenyl glycosides Arbutin (bearberry), Glucovanilline (Vannila Spp)

Anthraquinone Sennoside (Senna)

Flavone Hespiridin (Orange and lemon)

Cyanogenic Visnagin (Ammi visnaga)

Glucoalkaloids Solasodine (Solanum)

Steroid (Cardiac) Digitoxigenin (Digitalis)

Saponins Dioscorin (Dioscorea)

Coumarin Umbelliferone (Asafoetida)

Identifications tests General test for glycoside Specific tests for certain glycoside

Class or Type Chemical testsAnthraquinone 1. Borntrager’s test

2. Modified Borntrager’s test

Flavone (Flavonoids) Shinoda test

Cyanogenic Grignard’s test

Steroid (Cardiac) 1. Legal’s test2. Baljet’s test3. Keller-Killiani’s test

Saponins 1. Foam test2. Haemolytic test

Coumarin U.V. light test

Therapeutic effects and pharmaceutical application

Depends on chemical type of glycosides vary in effects and uses;

Example of glycoside Effects/Uses/Application Sennoside, aloin laxative

Digitoxin, strophanthin Cardiotonic

Sinigrin (Black mustard) GIT irritant

Salicin (Salix Spp.) Anti-rheumatic

Glycyrrhetinic acid Anti peptic ulcer

Hespiridin Capillary fragility

Methyl salicylate (Gaultheria) analgesic

Terpenoids

The term terpene represents hydrocarbons (C5H8)n, while,terpenoids hydrocarbons as well as, their oxygenated derivatives (alcohols, ketones, aldehydes).

Occurrence

Terpenes and terpenoids found in all volatile oils (essential oils) of plant or animal origin.

Distribution in plants

Rhizome e.g. gingerFruits e.g. carawayLeaves e.g. geraniumBud e.g. cloveWood e.g. sandalFlower e.g. rose, jasmin

Volatile oils and their terpenoid

Volatile oils Terpenoids presentFennel oil Anethol

Ginger oil Zingiberone

Clove oil Eugenol

Sandal wood Santalol

Peppermint oil Menthol

Lemon oil Limonene

Classification

Class or Type Examples Monoterpenes Citral (Lemon), menthol (pipermint), camphor

(eucalyptus)

Sesquiterpenes Farnesol (Fennel)

Diterpenes Santonin (Sandal)

Triterpenes Cholesterol

Tetraterpenes Lanosterol

Pentaterpenes --

Polyterpenes Rubber

Therapeutic effects and pharmaceutical application

Terpenoids have great importance in perfumery, cosmetics, soaps, incense stick, foods, pharmaceutical beverage industries

Therapeutically they exert wide spectrum of activities such as, antiseptic, stimulant, carminative, diuretic, anthelmintic, analgesic, antirheumatic, aromatic, counter irritant

Also used as insect repellant, insecticides, pesticides and deodorants

Volatile Oil

The odorous volatile, principles of plant and animal sources are known as volatile oils.

Occurrence

They are present in entire plant or in any part of the plant

They secreted in special structures such as ducts, cells, schizogenous or lysigenous glands, trichomes etc

They are commonly found in the species of labiatae, rutaceae, piperaceae, zingiberaceae, myrtaceae and lauraceae

Distribution in plants

All parts e.g. lemon-grassRhizome e.g. gingerFruits e.g. nutmeg, aniseLeaves e.g. eucalyptusBud e.g. cloveWood e.g. sandalFlower e.g. lavender

Properties

Odorous Volatile at room temperature They derived from terpenesand theire oxygenated

compounds terpenoids. They represents essence or active constituents of

plants hence called ‘essential oils’ They are mixtures of terpenes and terpenoids Lighter than water Have high refractive index Are optically active

Extraction, purification andIsolation of volatile oils

Hydro-distillation

Enfleurage

Ecuelle

Liquid carbon dioxide

Classification

Type of volatile oil Example Hydrocarbon Black pepper

Alcohol Cardamom, coriander

Aldehyde Cinnamon

Ester Gaultheria, lavender

Ketone Spearmint

Oxide Chenopodium

Phenolic-ether Anise

phenol clove

Identification test

TS of volatile oil containing crude drug + Sudan red III, gives red color to oil cells

TS of volatile oil containing crude drug + tincture of alkana, gives red color to oil globule

volatile oil + organic solvent ---> misciblevolatile oil + water---> Immiscible

Therapeutic effects and pharmaceutical application

Used as a flavouring agents and perfuming agent in pharmaceutical formulations, food, beverages and cosmetics

Also used as medicaments as;Volatile oil containing plant Use/application Umbelliferous fruits, cinnamon Carminative

Chenopodium Anthelmintics

Juniper Diuretics

Eucalyptus Antiseptics

Clove Dental analgesics

Jatamansi Sedative

Turpentine Local irritant

Tannins

A tannin is an astringent, bitter plant poly-phenolic compound that binds to and precipitates proteins.

Occurrence

They are widely distributed in plants. Most families of dicot contain tannin-free

species The best known families of which all species tested

contain tannin are: Aceraceae, Actinidiaceae, Anacardiacea, Bixaceae, Burseraceae, Combretaceae, Dipterocarpaceae, Ericaceae, Grossulariaceae, Myricaceae for dicot and Najadaceae and Typhaceae in Monocot.

Distribution in plants

Bark e.g. arjuna, ashoka Fruits e.g. amla, behadaLeaves e.g. teaSeed e.g. coffeeExtract e.g. Pale catechu and

black catechu

Properties

Soluble in water, polar organic solvents and Alkali solutions.

React with FeCl3 (bluish or greenish color) as they are Phenolic.

Precipitate proteins and Gelatin.

Form complex with alkaloids, heavy metals.

Extraction

There is no single method for extracting tannins from all plant material.

The procedures used for tannins are widely different.

The acetone is used as a solvent for the extraction of tannins.

Classification

True Tannins(High molecular weight compounds)

Hydrolysable Tannins(Pyrogallol)

Condensed Tannins(Catechol)

PseudotanninsLow molecular weight compounds

e.g. Gallic acid, Flavan-3,4-diol

Identification test

1. FeCl3Hydrolysable tannins Bluish colour.Condensed tannins Greenish colour.

2. Goldbeater’s Skin test (Ox-Intestine)Soak piece of Goldbeater’s skin in 2% HCl, wash with

water, soak in test solution, wash with water, finally soak with FeSO4 Brown or Black colour.

3. Gelatin testTannins + 1% Gelatin solution in NaCl white precipitate

Therapeutic effects and pharmaceutical application

1) Anti-oxidant2) Anti-diarrheal3) Antidote for heavy metals poisoning4)Treatment of burns, ulcers, inflammations4) Astringent to stop bleeding (hemorrhage)5)Treatment of Hemorrhoids6) Tanning industry

Resin

The term ‘resin’ is applied to more or less solid, amorphous products of complex chemical nature.

Occurrence

Mostly all natural resins occurs from plant source.

Distribution in plants

Rhizome e.g. gingerFruits e.g. capsicum Plant exudates e.g. myrrh, asafoetidaRoot e.g. jalapSeed e.g. kala dannaFlower e.g.

Properties

On heating they soften and finally melt. They are insoluble in water and usually insoluble in

petroleum ether but dissolve more or less completely in alcohol, chloroform and ether.

Chemically, resins are complex mixtures of resin acids, resin alcohols (resinols), resin phenols (resinotannols), esters and chemically inert compounds known as resenes.

Resins burn with a characteristic, smoky flame. Resins are often associated with volatile oils (oleoresins),

with gums (gum-resins) or with oil and gum (oleo-gum-resins).

Extraction, purification andIsolation of volatile oils

By extraction with alcohol and precipitation with water, e.g. Jalap, podophyllum, capsicum resin, ginger resin

By distillation for separation of oil, e.g. Colophony

By heating plant part, e.g. Guaiacum As plant exudates by incision, e.g. Myrrh,

asafoetida, balsam By collecting fossil resin, e.g. kauri

Classification

Type or class Example 1. Acid resin Myrrh, colophony

2. Ester resin Benzoin, storax

3. Resin alcohol Balsam

a. Oleo resin Canada balsam, ginger, capsicum

b. Oleo gum resin Asafoetida, guggul

c. Glyco resin Jalap, kala danna, turpentin

d. resenes Gutta purcha

4. Balsam resin Balsam of tolu

Therapeutic effects and pharmaceutical application

Natural plant resins were once valued for the production of varnishes, adhesives, and food glazing agents.

Provide constituents of incense and perfume. Is used to flavour wine.

A glazing agent is a natural or synthetic substance that provides a waxy, homogeneous, coating to prevent water loss from a surface and provide other protection