Local anti-infective agents and Preservatives - Medicinal Chemistry III B. Pharma 6th Semester

Local anti-infective agents and Preservatives


       Anti-infective agents – classification 

       Local Anti-infective agents – Introduction & Classification

       Mode of action of various Local Anti-infective agents

       Synthesis  and specific uses of Furazolidone

       Preservatives – Ideal characteristics & types

Learning Objectives

At the end of this lecture, student will be able to

Describe the term “anti-infective agent”

Classify anti-infective agents

Enlist the ideal characteristics of Local anti-infective agents (Germicides) & Preservatives

Classify Germicides & Preservatives

Describe the mode of action of Germicides

Introduction and Classification of anti-infectives

       Anti-infective agents are those agents which are used in the treatment of infectious diseases

       Selective toxicity is the main aim of modern “anti-infective therapy”


       Anti-infective agents may be classified according to a variety of schemes, as the chemical type of the compound the biological property and therapeutic indication

       A combination of these classification schemes is used to classify the anti-infective agents as

Classification of anti-infectives

Ø  Local Anti-infective agents:-

       Alcohols  - ethanol, isopropyl alcohol

       Phenols  - p-chlorophenol, hexachlorophene, resorcinol, hexyl resorcinol

       Halogen – containing compounds- Iodine tincture, Halozone.

       Oxidizing agents – Hydrogen peroxide, Benzoyl peroxide.

       Cationic surfactants – Benzalkonium chloride, Cetyl pyridium chloride

       Dyes – gentian violet, Methyene blue.

       Nitrogen compounds – Nitrofurazone, Furazolidone.

       Mercury compounds – Nitromersol and Thimerosal

Ø  Preservatives :-

       p-hydroxy benzoic acid derivatives – Methyl paraben, etc.,

       Miscellaneous compounds as chlorobutanol, etc.,

Ø  Anti-fungal agents :-

       Anti-fungal antibiotics – Nystatin, Candicidin, Hamycin, Griseofulvin, Amphotericin – B.

       Synthetic anti-fungal agents

       Substituted imidazoles: Clotrimazole, Metronidazole, Ketoconazole.

       Miscellaneous compounds- Zinc propionate, Sodium Caprylate, Tolnaftate.

Ø  Urinary tract anti-infectives :-

       Quinolones – Nalidixic acid, Norfloxacin, Ciprofloxacin, Perfloxacin

       Miscellaneous – Nitrofurantoin.

Ø  Anti-tubercular agents:-

       Synthetic anti-tubercular agents- PAS, INH, Ethanbutol, Pyrazinamide, etc.,

       Anti-tubercular antibiotics – Cycloserine, Rifampicin.

Ø  Anti-viral agents:- as

       Amantadine HCl, Acyclovir, Zidovudine

       Anti-AIDS – Azathymidine, Suramin.

Ø  Anti – protozoal agents:- 

       Metronidazole, Iodoquinol, Dimercaprol

Ø  Anthelmintics:-

       Diethyl Carbamazine, Mebendazole, Niclosamide

       Anti-scabious & anti-pedicular agents:-

       Benzyl benzoate, Diethyl toluamide, Lindane.

Benzyl Benzoate

Diethyl toluamide


Local Anti-infective agents (Germicides)

There are two primary sub-types

Antiseptics:- kill (-cidal) or prevent the growth of (-static) micro-organisms when applied to living tissues.

Ø  A useful antiseptic must –

       Have low toxicity so that it can be used directly on skin or wounds.

       Have a rapid and sustained lethal action against micro-organisms.

       Have low surface tension, so that it will spread into the wound.

       Have the ability to retain activity in the presence of body fluids including pus.

       Be non-irritating to tissues & non-allergic

       Lack systemic toxicity when applied to the skin or mucous membrane.

       Have no interference with the healing process of the wound.


Ø  A disinfectant is an agent that prevents transmission of infection by the destruction of pathogenic micro-organisms when applied to inanimate objects.

Ø  An ideal disinfectant:-

       Exerts a rapid lethal action against all potentially pathogenic microorganisms & spores.

       Have good penetrating properties into organic matter.

       Should be compatible with organic compounds (particularly soaps).

       Is not inactivated by living tissues.

       Is non-corrosive

       Is esthetically pleasing (non-staining or odorless)

Alcohols and related compounds:-

       Antibacterial action is due to their ability to denature the bacterial proteins & inhibit phosphorylation systems


       Clear, Colorless, Volatile liquid, Burning taste, Characteristic pleasant odor



        Mild counterirritant

       Rubbing alcohol is used as an

ü   Astringent

ü   Rubefacient

ü  Mild local anesthetic

Isopropyl Alcohol

       Suitable substitute for ethanol

       But must not be ingested

       Primarily as a disinfectant for the skin and for surgical instruments

       Bactericidal in the concentration range of 50% to 95%

       A 40% concentration is considered equal in antiseptic efficacy to a 60% ethanol in water solution

Formaldehyde Solution

       Formalin is a colorless aqueous solution

       Used as a disinfectant for surface sterilization

       Contains not less than 37% w/v of formaldehyde (HCHO) with methanol added to retard polymerization

       The germicidal action of formaldehyde is slow but powerful

       The mechanism of action: denaturation of proteins

ü  Direct nonspecific alkylation of nucleophilic functional group (amino, hydroxyl, and sulfhydryl) in proteins and nucleic acids to form carbinol derivatives

       Gutaraldehyde used to sterilize surgical instruments and surfaces contaminated with hepatitis virus


       Phenol (carbolic acid) is a colorless to pale-pink crystalline material with a characteristic “medicinal odor

       Liquified phenol is simply phenol containing 10% water

       Bacteriostatic conc- 0.5%, Bactericidal-1%, fungicidal 1.5%

       MOA: denaturation of proteins

       Phenols & derivatives:-


       p-Chlorophenol is used in combination with camphor in liquid petrolatum as an external antiseptic and anti-irritant


       Hexachlorophene, 2,2-methylene bis (3,4,6-trichlorophenol)

       2,2- dihydroxy-3,5,6,3,5, 6-hexachlorodiphenylmethane

       Hexachlorophene is easily adsorbed onto the skin and Enters the sebaceous glands

       Topical application elicits a prolonged antiseptic effect

       Hexachlorophene is used in concentrations of 2% to 3% in


       Detergent creams



       For various antiseptic uses

       Effective against gram-positive bacteria

       Many gram-negative bacteria  are resistant


       m- Dihydroxybenzene (resorcin)

       Resorcinol is only a weak antisepticit is used in 1% to 3% solutions

       Ointments and pastes in concentrations of 10% to 20% for the treatment of skin conditions

ü  Ringworm

ü  Eczema

ü  Psoriasis

ü  Seborrheic

ü  Dermatitis

        Keratolytic agent



       Effective antiseptic

       Bactericidal and fungicidal properties

Oxidizing agents:-

       Oxidizing agents that are of any value as germicidal agents depend on their ability to liberate oxygen in the tissues

       MOA: oxidation of sulphydryl groups of bacterial enzymes

       Hydrogen peroxide  - H2O2

       Disinfectant and sterilant

       Benzoyl peroxide is both keratolytic and keratogenic

        It is used in the treatment of acne- exfoliant ,sebostatic

        Benzoyl peroxide induces proliferation of epithelial cell leading to sloughing and repair

Halogen – containing compounds:

Iodine tincture

       It is usually 2–7% elemental iodine, along with potassium iodide or sodium iodide, dissolved in a mixture of ethanol and water. 

       It contains iodine which is an antiseptic. It is for use on minor wounds, cuts and scrapes.


       Charge-transfer complex of iodine with the nonionic surfactant PVP (poly vinyl pyrrolidine)

       Povidone–iodine is used as an aqueous solution for pre-surgical disinfection of the incision site

       Treating  infected wounds and damage to the skin

       It is effective for local bacterial and fungal infections

Chlorine- Containing compounds

       All the chlorophores act by releasing chlorine which oxidezes the sulphydryl groups of bacterial enzymes and deactivates certain bacterial enzymes

       These compounds release hypochlorous acid when dissolved in water in the presence of acid – i.e HOCl is the active germicidal species.

        HOCl generates nascent oxygen to destroy the vital cellular machinery of microorganism


       Chlorhexidine, also known as chlorhexidine gluconate (CHG), is a disinfectant and antiseptic that is used for skin disinfection before surgery and to sterilize surgical instruments-used both to disinfect skin of the patient and the hands of the healthcare providers.

       It is a germicidal mouthwash that reduces bacteria in the mouth. Chlorhexidine gluconate oral rinse is used to treat gingivitis (swelling, redness, bleeding gums).


       P-dichlorosulfamoylbenzoic acid

       Faint chlorine odor

       The sodium salt of halazone is used to disinfect drinking water

Cationic surfactants:-

All cationic surfactants are quaternary ammonium compounds. They are always ionized in water and exhibit surface active properties.

They form micelles by concentrating at the interface of immiscible solvents-cationic head group has a high affinity for water and long hydrocarbon tail has an affinity for lipids and nonpolar solvents

       Benzalkonium chloride [Alkyl Benzyl dimethyl ammonium chloride is a mixture of alky benzyl dimethyl ammonium chloride]

       Benzalkonium chloride is a detergent, an emulsifier  and a wetting agent

       It is used as an antiseptic for skin and mucous membranes

       Cetyl pyridinium chloride

       It is used as a general antiseptic for  intact skin

       Irrigation of mucous membranes



Gentian violet [Hexamethyl-p-rosaniline chloride](crystal violet,methyl violet)

       Antiseptic dye used to treat fungal infections of the skin (e.g., ringworm, athlete's foot).

       Also has weak antibacterial effects and may be used on minor cuts and scrapes to prevent infection.

Methylene blue [3,7-Bis(dimethylamino)-Phenazathonium chloride

       Weak antiseptic properties(bacteriostatic)

       Treatment of cystitis  & urethritis

Nitrogen Compound:

Nitrofuran derivatives

       Nitrofurazone: [5-Nitro-2-furfuraldehyde semicarbazone]

       Furazolidone {3-[(5-nitrofurylidene) amino]-2-oxazolidinone}

       Has bactericidal action against a relatively broad range of intestinal pathogens including S.aureus, E.coli, Salmonella, Shigella, Proteus, Enterobacter and Vibriocholerae.

       Also active against the protozoan Giardia Lamblia.

       Used orally in the treatment of bacterial or protozoal diarrhea caused by susceptible organisms.

Mercury compounds:


       From early days, mercurial were used to treat skin infections & syphilis

       MOA: reversible nature of sulfhydryl group blockage

       Nitromersol [3-(hydroxy mercuri)-4-nitro-o-cresol]

       Thimerosal {sodium [(o-carboxy phenyl) thio] ethyl mercury}

Mode of Action

Alcohols and related compounds:-

       Ability to denature proteins &  inhibit phosphorylation systems

       As the primary alcohol chain length increases, vanderwaal’s interactions increase and the ability to penetrate microbial membranes increases.

       As water solubility decreases the apparent anti-microbial potency diminishes. Branching of the alcohol chain decreases anti-bacterial potency. Weaker vanderwall’s forces brought about by branching do not penetrate bacterial cell membranes as efficiently. Yet, 2-propanol is used commercially instead of n-propyl alcohol as it is less expensive.

       The germicidal action of formaldehyde is slow but powerful. It is the direct, non-specific alkylation of nucleophilic functional groups (amino, hydroxyl, sulphydryl) in proteins and nucleophilic acids to form ‘Carbinol’ derivatives.

Phenols and Derivatives:-

       Phenols  “denatures bacterial proteins at low concentrations”, “lysis of bacterial cell membranes at higher concentrations”

Oxidizing agents:-

       Germicidal action is based on their ability to liberate oxygen in the tissues.

       All these react in the tissues to generate oxygen and oxygen radicals. Oxidizing agents are especially effective against anaerobic bacteria and can be used in cleansing contaminated wounds.

Halogen-containing compounds:-

       Iodine acts to inactivate proteins by iodination of aromatic residues (Phenyl alanyl and tyrosyl) and oxidation (sulphhydryl groups).

       Chlorine released from compounds (Halozone) act by chlorination of amide nitrogen atoms &oxidation of sulfhydryl groups in proteins

Cationic Surfactants:-

       The mechanism of action involves the dissolution of the surfactant into the microbial cell membrane, destabilization and subsequent lysis.

       The surfactants may also interfere with enzymes associated with the cell membrane.


       Acts on cell membranes. The difference in the susceptibility is related to the cellular characteristics. The cationic dyes are active against gram +ve bacteria and many fungi; gram –ve bacteria are generally resistant.


       The mechanism of action of Nitrofurans are not fully understood.

       These Nitrofurans are known to be mutagenic and carcinogenic under certain conditions. The cellular effects may be due to DNA damage caused by metabolic reaction products.


Ø  “Preservatives are added to various dosage forms and cosmetic preparations to prevent microbial contamination”

Ø  In parenteral and ophthalmic preparations, preservatives are used to maintain sterility in the event of accidental contaminations during use.

Ø  Ideal preservative should be

       Effective at low concentrations against all possible microorganisms


       Compatible with other  constituents used in the preparation

       Stable for the shelf life of the preparation.

Ideal preservative does not exist – most preservatives have some ideal features

       The preservatives are of 2 types

Ø  Para-hydroxy benzoic acid derivatives

Ø  Miscellaneous.

p-hydroxybenzoic acid derivatives (Parabens):-

       Esters of p-hydroxy benzoic acid have anti-fungal properties. Their toxicity to human host is generally low due to rapid hydrolysis to p-hydroxy benzoic acid, which is rapidly conjugated and excreted.

       Used as preservatives for liquid dosage forms

       Preservative effect increase with increase in molecular weight, but the methyl ester is more effective against ‘Molds’, where as the propyl ester is more effective against ‘Yeasts’.

       Eg, Methyl paraben – Methyl-p-hydroxybenzoate.

Others are propyl paraben (Propyl-p-hydroxybenzoate), Ethyl paraben (Ethyl-p-hydroxybenzoate) and Butyl paraben (Butyl-p-hydroxybenzoate)

Other preservatives:-

       Chlorobutanol: - 1,1,1-Trichloro-2-Methyl-2-Propanol

       Used as bacteriostatic in injections, ophthalmics & intranasal preparations

       Sodium benzoate-preservative in acidic liquid preparations

       Phenyl carbinol- used in ointments & lotions as an antiseptic in the treatment of pruritic infections

       Sodium propionate, Benzyl alcohol, Phenyl ethyl alcohol (2-Phenyl ethanol), Benzoic acid, Phenyl mercuric nitrate, Phenyl mercuric acetate, etc

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