Fungal squalene epoxidase (inhibitor). [1]

In fungal cells and cell extracts, tolnaftate (NP-27) inhibits the formation of sterols, leading to a buildup of squalene. The direct suppression of Candida albicans' microsomal squalene epoxidase [1] verified this mechanism of action. Tolnaftate (NP-27) inhibits the formation of sterols and releases up to 30% of intracellular [14C]aminoisobutyric acid at a dose of 100 µM [2].

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Tolnaftate inhibited sterol (ergosterol) biosynthesis in fungal cells and cell-free extracts.
In Trichophyton mentagrophytes cells, tolnaftate caused a dose-dependent inhibition of [¹⁴C]acetate incorporation into sterols and a concomitant accumulation of radioactivity in squalene. At 0.1 mg/L, it caused essentially complete blockade of squalene epoxidation, with 96.7% of incorporated radioactivity found in squalene. No accumulation was seen in 4-methylsterols or 4,4-dimethylsterols, ruling out inhibition of steps after squalene epoxidation. [1]
In Candida albicans whole cells, tolnaftate inhibited ergosterol biosynthesis, causing accumulation of radioactivity in squalene only. However, inhibition was incomplete even at concentrations up to 100 mg/L. The concentration causing 50% inhibition (IC₅₀) in whole cells was 0.25 ± 0.05 mg/L, while the concentration for 95% inhibition was >100 mg/L. [1]
In cell-free extracts of C. albicans, tolnaftate was more potent, with an IC₅₀ of 0.13 ± 0.03 mg/L and an IC₉₅ of 10.0 ± 1.5 mg/L for ergosterol biosynthesis inhibition. [1]
Tolnaftate directly inhibited microsomal squalene epoxidase from C. albicans with an IC₅₀ of 0.32 ± 0.12 mg/L and an IC₉₅ of 12.5 ± 3.8 mg/L. [1]
In C. albicans whole cells, the inhibitory effect measured by [¹⁴C]acetate incorporation was less pronounced at pH 4.5 compared to pH 6.5 (e.g., at 10 mg/L, inhibition to 16.7% vs 9.7% of control, respectively). [1]
Rat liver cell-free cholesterol biosynthesis was much less sensitive, with tolnaftate causing only 58.9% inhibition at 100 mg/L. [1]

Squalene epoxidase (EC 1.14.99.7) activity was assayed using microsomal preparations from Candida albicans in the presence of soluble cytoplasm.
The assay measured the conversion of squalene to squalene epoxide, which is a key step in ergosterol biosynthesis. The inhibitory effects of tolnaftate and other compounds on this enzyme were evaluated in this cell-free system. [1]

Ergosterol biosynthesis in fungal cells was measured by incubating cells (e.g., Candida albicans, Trichophyton mentagrophytes) with radioactive precursors.
For whole-cell assays, cells were incubated for 2 hours with [U-¹⁴C]acetate at pH 6.5. After incubation, nonsaponifiable lipids were extracted, separated by thin-layer chromatography, and the radioactivity in different fractions (e.g., ergosterol, squalene) was counted to assess the biosynthetic flux and the site of inhibition.
An alternative method in whole cells measured the incorporation of radioactivity from L-[methyl-¹⁴C]methionine into the sterol side chain via the sterol methylation reaction, which assesses later steps in the pathway.
For cell-free assays, ergosterol biosynthesis was measured in cell extracts of C. albicans by incorporation of [2-¹⁴C]mevalonate, a more direct precursor. [1]

Effects During Pregnancy and Lactation
◉ Overview of use during lactation
The safety of topical tonaphthyl ester during lactation has not been studied, and there is no data on its absorption after topical application. Because its absorption after topical application may be poor, it is considered to pose a low risk to breastfed infants. Avoid application to the nipple area and ensure that the infant's skin does not come into direct contact with the skin area where the medication has been applied. Only water-soluble creams, gels, or liquid products should be applied to the breast, as ointments may expose the infant to high concentrations of mineral oil through licking. [1] ◉ Effects on breastfed infants
No published information was found as of the revision date. ◉ Effects on breastfeeding and breast milk
No published information was found as of the revision date.

[1]. Ryder, N.S., I. Frank, and M.C. Dupont, Ergosterol biosynthesis inhibition by the thiocarbamate antifungal agents tolnaftate and tolciclate. Antimicrob Agents Chemother, 1986. 29(5): p. 858-60.

[2]. Georgopapadakou, N.H. and A. Bertasso, Effects of squalene epoxidase inhibitors on Candida albicans. Antimicrob Agents Chemother, 1992. 36(8): p. 1779-81.

Crystals or white powder. (NTP, 1992)
Tinactin is a monothiocarbamate, a (3-tolyl)aminothiomethyl ester of 2-naphthol. It is a synthetic antifungal agent used to treat tinea cruris, tinea pedis, and tinea corporis. It is an antifungal drug whose function is related to 2-naphthol.
Tinactin is a synthetic over-the-counter antifungal agent. It can be in the form of cream, powder, spray, or liquid aerosol for the treatment of tinea cruris, tinea pedis, and tinea corporis. It is sold under many brand names, most commonly Tinactin and Odor Eaters.
Tinactin is a thiocarbamate derivative with bactericidal or bacteriostatic effects. Tonaactin is a selective, reversible, non-competitive membrane-bound squalene-2,3-cyclooxygenase inhibitor, an enzyme involved in the biosynthesis of ergosterol. Inhibition leads to squalene accumulation and ergosterol (an important component of the fungal cell wall), thereby increasing cell membrane permeability, disrupting cell structure, and causing cell death. In addition, this drug may also deform hyphae and inhibit the hyphal growth of susceptible fungi. A synthetic antifungal agent. See also: tonaphthyl; triclosan (ingredient). Drug Indications Topical tonaphthyl is used to treat skin infections such as tinea pedis, tinea cruris, and tinea corporis. Tonaphthyl may also be used in combination with other antifungal drugs to treat infections of the nails, scalp, palms, and soles. Powder and powder aerosol are available for the prevention of tinea pedis. Mechanism of Action Tonaphthyl is a topical fungicide. While its exact mechanism of action is not fully understood, it is believed to inhibit the biosynthesis of ergosterol by inhibiting squalene epoxidase. It has also been reported to deform hyphae and inhibit the hyphal growth of susceptible organisms. Pharmacodynamics Tonaphthyl is a synthetic, over-the-counter antifungal drug.

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Tobramycin (O-2-naphthyl-m,N-dimethylthiocarbamate) is a thiocarbamate antifungal drug.
It has selective activity against dermatophytes and is used clinically as a topical treatment for dermatophyte infections.
Its main mechanism of action is the inhibition of fungal squalene epoxidase (a key enzyme in ergosterol biosynthesis), leading to squalene accumulation and ergosterol depletion. This mechanism is similar to that of allylamine antifungal drugs (such as terbinafine).
There is a strong correlation between its antifungal activity and the inhibition of ergosterol biosynthesis, which strongly suggests that this is its main mechanism of action. However, the existence of other mechanisms cannot be ruled out. [1]

C19H17NOS

307.41

307.103

2398-96-1

Tolnaftate-d7;1329835-64-4

5510

White to off-white solid powder

1.2±0.1 g/cm3

453.4±38.0 °C at 760 mmHg

110.5-111.5ºC

228.0±26.8 °C

0.0±1.1 mmHg at 25°C

1.697

5.15

0

2

3

22

386

0

FUSNMLFNXJSCDI-UHFFFAOYSA-N

InChI=1S/C19H17NOS/c1-14-6-5-9-17(12-14)20(2)19(22)21-18-11-10-15-7-3-4-8-16(15)13-18/h3-13H,1-2H3

O-naphthalen-2-yl N-methyl-N-(3-methylphenyl)carbamothioate

Tinactin, Tinaderm, Aftate; NP-27, NP 27, NP27

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~50 mg/mL (~162.65 mM)
H2O : < 0.1 mg/mL

Solubility in Formulation 1: ≥ 3.25 mg/mL (10.57 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 32.5 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 3.25 mg/mL (10.57 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 32.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 3.25 mg/mL (10.57 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 32.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)