LECTURE 4

PHARMACEUTICAL CHEMISTRY IHS 2016

09/02/2016

ANTIFUNGALS • Classification and nomenclature; • Structures of selected antifungal agents; • Physical and chemical properties • Pharmaceutical applications

• The use of antifungal drugs in treatment of infections are common.

• There are used in a lot of infections• Some are active orally , some topically as

ointments , cream, lotions and suspensions

Classification They can be broadly classified into two categories • Chemical antifungal agents • Antibiotics

CHEMICAL ANTIFUGAL AGENTS A number of chemical agents have antibacterial- antifungal properties .

The simplest are aromatic acid • Benzoic acid • Salicylic acid

BENZOIC ACID

CHEMICAL STRUCTURE• The chemical formula of benzoic acid is C7H6O2: • it has seven carbon (C) atoms hydrogen (H)

atoms and two oxygen (O) atoms. • This chemical formula can also be written as

C6H5COOH. On the above structure The chemical structure of carboxylic acid on the left indicates all the carbon and hydrogen atoms on the benzene ring.

• Benzoic acid is an organic compound because it contains carbon,

• it is also an aromatic carboxylic acid. It is aromatic because it has a benzene ring in its chemical structure.

• Benzene is aromatic because it has alternating double bonds between each carbon.

• It's classified as a carboxylic acid because it has a carboxyl group in its structure, which is the COOH group boxed in red.

PROPERTIES• Benzoic acid is a solid that is crystalline in

appearance, similar to white needles.• It is sparingly soluble in cold water and more

soluble in hot water. • Soluble in chloroform, alcohol, ether and alkali

hydroxide .• A natural source of benzoic acid is gum benzoin,

which comes from certain tree barks; however, benzoic acid can also be made by synthetic means.

• it is stable and gives a buff colored precipitate with ferric salt ,

• It forms insoluble salts with heavy metals like silver, led ,mercury etc.

Use• Benzoic acid is used externally as antiseptic in

lotions , mouth washes etc.• It can be used in combination with salicydic

acid to act as a antifungal agents • It is officially known as Whitefield's ointment • It is an effective food preservative as an acid

and as sodium salt.

SALYCYLIC ACID

• is a monohydroxybenzoic acid- a type of phenolic acid and a beta hydroxy acid.

• Salicylic acid has the formula C6H4(OH)COOH, where the OH group is ortho to the carboxyl group. It is also known as 2-hydroxybenzoic acid

PROPERTIES • It occurs as a white crystalline or fluffy powder with

sweetish taste.• It is slightly soluble in water and soluble in organic

solvent and alkali hydroxides.• It produces violet colour with ferric salts. • Coloured compounds are produced with oxidizing

agents .• It forms salts with heavy metals. • It has a strong antiseptic properties. • It acts as an antifungal in 3% to 5 % in concentration

form of ointment , cream ,lotion.

• It contains both a hydroxyl and a carboxyl group, which react with either an acid or an alcohol.

• The carboxyl group forms esters with alcohols; e.g. methyl salicylate is formed with methanol, which used in food flavorings and preservatives; menthyl salicylate is formed with methanol, which is used in suntan lotions.

• The hydroxyl group reacts with acetic acid to form acetylsalicylic acid (called aspirin) which is the most widely common antiseptic and antipyretic agent.

• Phenyl salicylate is formed with phenol, which is also used as an antiseptic and antipyretic agent SALYCYLIC ACID .

Use Salicylic acid is a keratolytic. It belongs to the same class of drugs as aspirin (salicylates). It works by increasing the amount of moisture in the skin and dissolving the substance that causes the skin cells to stick together. This makes it easier to shed the skin cells. Warts are caused by a virus. Salicylic acid does not affect the virus.

CLOTRIMAZOLE

An imidazole derivative with a broad spectrum of antimycotic activity. It inhibits biosynthesis of the sterol ergostol, an important component of fungal cell membranes. Its action leads to increased membrane permeability and apparent disruption of enzyme systems bound to the membrane.

PROPERTIES• It is a yellow odorless powder • It is insoluble in water , soluble in alcohol and

chloroform• It is stored in a closed container , protected

from light UseIt is used as cream and pessaries in the treatment tinea infections and candidiasis by candida abicans .

MICONAZOLE• Miconazole is a synthetic antifungal agent

belonging to the imidazole group.• C18H14Cl4N20

PROPERTIES• It is a white micro crystalline powder.• Slightly water soluble and more soluble in

acetone.• Odourless or almost odourless.

Use It is used in 2% creams to be applied topically for treatment of fungal infections.

ANTIBIOTICS These are substances that are effective orally as antifungal agents.• Amphoterin B• Candicin• Nystatin• Griseoflulvin

GRISEOFLULVIN

Formula:C17H17ClO6

PROPERTIES • Griseofulvin is an antifungal agent used in the

treatment of TINEA infections• It is a macrolide antibiotic• White to pale cream crystalline powder,

odourless or nearly odourless but bitter tasting.• Practically insoluble in water and sparingly

soluble in alcohol.

AMPHOTERIN B• Is a mixture containing amphoteric A and B

which the B component is more active.• Amphoterin B is large ring of atoms with a

cyclic ester ring, containing multiple conjugated carbon-carbon double bonds on one side of the ring and multiple hydroxyl.

PROPERTIESIs a Crystalline Yellow-orange powder with a faint odour and is water soluble.It is amphoteric in nature.It is unstable in aqueous medium and deteriorates rapidlyAmphotericin B is poorly water soluble .Amphotericin B acts by binding sterols in the cell membrane leading to the formation of transmembrane channels and subsequent ion leakage.

UsePolypeptide antibiotic active against gram positive bacteria. Antifungal.It is given parentally and topically for treatment of fungal infection

CANDICIDINProperties :Is a yellow powder , almost odourless and it is insoluble in water.It is kept in a air-tight container away from lightUse: it is used to treat viginal fungal infection

NYSTATINNystatin is a Polyene antifungal antibiotic complex containing 3 biologically active components, A1, A2, A3. Increases the permeability of the cell membrane of sensitive fungi by binding to sterols.

PROPERTIES Brown solidNystatin is polyene antifungal containing a conjugated tetraene and a diene, isolated as a complex of three components A1, A2 and A3 from Streptomyces noursei ,Nystatin, like most polyene antifungals, binds to sterols in the fungal cell membrane leading to formation of ion channels in the wall, ion imbalance and cell death.

LECTURE 5

ANTITUBERCULOSIS AGENTS • -Antiamoebics & anthelmintic• Antimalarials

STERIODS • NON Steroidal anti-inflammatory • analgesics and antipyretic