Tolnaftate

Description

Tolnaftate is a thiocarbamate antifungal agent. It is active against clinical isolates of the dermatophytes T. rubrum, T. mentagraphytes, T. verrucosum, E. floccosum, and M. canis (MIC₅₀s = 50, 100, 6, 50, and 50 ng/ml, respectively), as well as 18 additional yeast and filamentous fungi species (MIC = 0.003-0.8 μg/ml)., Tolnaftate also reduces aflatoxin production in A. parasiticus in a concentration-dependent manner. It inhibits squalene epoxidase with an IC₅₀ value of 12.5 μg/ml in a cell-free assay.

Chemical Properties

White Solid

Originator

Tinactin,Schering,US,1965

Uses

Tolnaftate is used to study the mechanism of ergosterol (sterol) biosynthesis at the rate-limiting step of squalene epoxidase inhibition. Tolnaftate is clinically used to treat cutaneous infections such as athlete?s foot, jock itch, and ringworm1. It also has been used as a comparator compound for antifungal efficiency studies.

Uses

Tolnaftate topical is used to treat skin infections such as athlete's foot, jock itch, and ringworm infections. Tolnaftate is also used, along with other antifungals, to treat infections of the nails, scalp, palms, and soles of the feet.

Uses

antifungal for cutaneous infections.
Tolnaftate (Aftate, Tinactin, etc.) is an odorless and nonstaining synthetic antifungal agent whose exact mechanism of action is unknown. It is effective against dermatophytes and P. orbiculare and Pityrosporum ovale. It is ineffective against C. albicans and bacteria.

Definition

ChEBI: A monothiocarbamic ester that is the methyl(3-tolyl)carbamothioate ester of 2-naphthol. A synthetic anti-fungal agent used to treat jock itch, athlete's foot and ringworm.

Indications

Tolnaftate (Aftate, Tinactin, etc.) is an odorless and nonstaining synthetic antifungal agent whose exact mechanism of action is unknown. It is effective against dermatophytes and P. orbiculare and Pityrosporum ovale. It is ineffective against C. albicans and bacteria.

Manufacturing Process

In a first step, 2-naphthol is reacted with thiophosgene to give 2-naphthyl chlorothionoformate.
A mixture of 4.0 grams of N-methyl-3-toluidine and 2.8 grams of sodium hydrogencarbonate in 50 cc of acetone was stirred at 0° to 10°C and 7.4 grams of 2-naphthyl chlorothionoformate was added in small portions thereto and the mixture was heated under reflux for 30 minutes. The cooled mixture was poured into about 150 cc of cold water and 2-naphthyl-N-methyl-N-(3- tolyl)thionocarbamate was obtained as white crystals. Yield is 9.1 grams (90%). Recrystallization from alcohol gave colorless needle crystals, MP 110.5° to 111.5°C.

Therapeutic Function

Antifungal

General Description

Crystals or white powder.

Air & Water Reactions

Thio and dithiocarbamates slowly decompose in aqueous solution to form carbon disulfide and methylamine or other amines. Such decompositions are accelerated by acids. Insoluble in water.

Reactivity Profile

Tolnaftate is a thiocarbamate. Flammable gases are generated by the combination of thiocarbamates and dithiocarbamates with aldehydes, nitrides, and hydrides. Thiocarbamates and dithiocarbamates are incompatible with acids, peroxides, and acid halides.

Health Hazard

SYMPTOMS: In susceptible persons, Tolnaftate may cause sensitization or irritation.

Fire Hazard

Flash point data on Tolnaftate are not available, Tolnaftate is probably combustible.

Clinical Use

Tolnaftate (Tinactin, others) is a nonprescription antifungal agent effective in the topical treatment of dermatophyte infections and tinea. The mechanism of action is unknown.

Clinical Use

O,2-Naphthyl m,N-dimethylthiocarbanilate (Tinactin,Aftate, NP-27) is a white crystalline solid that is insoluble inwater, sparingly soluble in alcohol, and soluble in most organicsolvents. The compound, a thioester of β-naphthol, isfungicidal against dermatophytes, such as Trichophyton,Microsporum, and Epidermophyton spp., that cause superficialtinea infections. Tolnaftate is available in a concentrationof 1% in creams, powders, aerosols, gels, and solutionsfor the treatment of ringworm, jock itch, and athlete’s foot.Tolnaftate has been shown to act as an inhibitor of squaleneepoxidase in susceptible fungi, so it is classified with theallylamine antimycotics. Tolnaftate is formulated into preparationsintended to be used with artificial fingernails to counteractthe increased chance of ringworm of the nail beds.

Safety Profile

Mtldly toxic by ingestion. An experimental teratogen. When heated to decomposition it emits toxic fumes of SOx and NOx. A fungicide used to control athlete's foot. See also ESTERS and CARBAMATES.

Synthesis

Tolnaftate, O-(2-naphthyl)-N-methyl-N-(3-tolyl)-thiocarbamate (35.4.9), is synthesized by reacting equimolar amounts of 2-naphthol and thiophosgene to make a monosubstituted product of thiophosgene (35.4.8), which is then reacted with N-methyl-3-toluidine to give the desired tolnaftate.