- Fungal lanosterol 14α-demethylase (key enzyme in ergosterol biosynthesis) [1]
- Fungal cell membrane integrity [1]

- Econazole is a broad-spectrum antimycotic with potent inhibitory activity against various fungi. It inhibited the growth of Candida albicans with a minimum inhibitory concentration (MIC) of 0.125 μg/mL [1]
- It showed activity against dermatophytes: MIC values were 0.0625 μg/mL for Trichophyton rubrum, 0.125 μg/mL for Microsporum canis, and 0.25 μg/mL for Epidermophyton floccosum [1]
- It suppressed the growth of Aspergillus fumigatus and Cryptococcus neoformans with MICs of 1 μg/mL and 0.5 μg/mL, respectively [1]
- The compound disrupted fungal cell membrane structure by inhibiting ergosterol synthesis, leading to increased membrane permeability and cell lysis [1]

- In guinea pig dermatophytosis model (induced by Trichophyton mentagrophytes): Topical application of Econazole (1% cream) twice daily for 7 days resulted in 90±3% clearance of skin lesions, with complete fungal eradication in 85% of animals [1]
- In mouse systemic candidiasis model (intraperitoneal inoculation of Candida albicans): Intraperitoneal injection of Econazole (20 mg/kg daily for 5 days) reduced fungal load in the kidneys by 78±4% and prolonged survival rate by 60% compared to the control group [1]

- Lanosterol 14α-demethylase inhibition assay: Fungal microsomal fractions (from Candida albicans) were incubated with Econazole (0.01–2 μg/mL) and lanosterol (substrate) at 30°C for 2 hours. The reaction product (4,4-dimethylcholesta-8,14,24-trien-3β-ol) was quantified by thin-layer chromatography (TLC) to evaluate enzyme inhibition efficiency [1]

- Fungal growth inhibition assay: Fungal strains (Candida albicans, Trichophyton rubrum, etc.) were inoculated into Sabouraud dextrose broth containing Econazole (0.03125–4 μg/mL) and incubated at 28°C for 48–72 hours. Fungal growth was assessed by measuring absorbance at 600 nm, and MIC values were determined as the lowest concentration inhibiting visible growth [1]
- Fungal cell membrane permeability assay: Candida albicans cells were treated with Econazole (0.25 μg/mL) for 24 hours, then stained with a membrane-impermeable fluorescent dye. Fluorescence intensity was measured by fluorometry to assess membrane disruption [1]

- Guinea pig dermatophytosis model: Guinea pigs were infected with Trichophyton mentagrophytes by topical application on shaved dorsal skin. Econazole was formulated as a 1% cream and applied topically twice daily for 7 days. Skin lesions were scored visually, and fungal cultures were performed to confirm eradication [1]
- Mouse systemic candidiasis model: Mice were intraperitoneally inoculated with Candida albicans (1×10⁶ CFU/mouse). Econazole was dissolved in polyethylene glycol and administered intraperitoneally at 20 mg/kg daily for 5 days. Kidneys were collected for fungal load quantification (CFU/g tissue) and survival was monitored for 14 days [1]

Absorption, Distribution and Excretion>
After topical application of econazole nitrate to the skin in normal subjects, systemic absorption was very low. Although most of the drug remained on the skin surface, the drug concentration detected in the stratum corneum was much higher than the minimum inhibitory concentration for dermatophytes.

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Metabolism/Metabolites>
Hepatic metabolism.
Hepatic metabolism.

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- Absorption: Very little transdermal absorption after topical application (≤5%); poor oral absorption (bioavailability <10%) [1]
- Distribution: After systemic administration, the drug is distributed to various tissues, with the highest concentrations in the liver and kidneys [1]
- Excretion: Mainly excreted in feces (65%) and urine (25%) in the form of unchanged drug and metabolites [1]

Toxicity Summary
Econazole interacts with 14α-demethylase, a cytochrome P-450 enzyme essential for the conversion of lanosterol to ergosterol. Since ergosterol is an important component of the fungal cell membrane, inhibition of its synthesis leads to increased cell permeability, resulting in leakage of cell contents. Econazole may also inhibit endogenous respiration, interact with membrane phospholipids, inhibit the conversion of yeast to mycelium, inhibit purine uptake, and impair the biosynthesis of triglycerides and/or phospholipids. Pregnancy and Lactation Effects ◉ Overview of Use During Lactation The safety of topical econazole during lactation has not been studied. The risk to nursing infants is low due to the absorption rate of less than 1% after topical application. [1] Avoid application to the nipple area and ensure that the infant's skin does not come into direct contact with the area where the medication has been applied. Only water-soluble creams or gels should be applied to the breast, as ointments may expose the infant to high concentrations of mineral oil through licking. [2]
◉ Effects on breastfed infants
No published information found as of the revision date.
◉ Effects on lactation and breast milk
No published information found as of the revision date.

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Toxicity Data
LD50: 462 mg/kg (oral, mouse) (A308)
LD50: 462 mg/kg (oral, rat) (A308)
LD50: 668 mg/kg (oral, guinea pig) (A308)
LD50: >160 mg/kg (oral, dog) (A308)

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- Acute toxicity: The oral LD50 and intraperitoneal LD50 in rats were >2000 mg/kg; the intraperitoneal LD50 in mice was 1200 mg/kg [1]
- Dermal toxicity: No irritation or sensitization was observed in the guinea pig skin irritation test of 1% econazole cream [1]
- Systemic toxicity: No significant changes in liver and kidney function or hematological parameters were observed in rats after subchronic administration (20 mg/kg/day for 28 days) [1]

[1]. Bilogical and toxicological properties of econazole, a broad-spectrum antimycotic. Arzneimittelforschung. 1975 Feb;25(2):224-30.

1-{2-(4-chlorobenzyloxy)-2-(2,4-dichlorophenyl)ethyl}imidazolium belongs to the imidazolium class of compounds. Its structure is similar to 1-(2,4-dichlorophenyl)-2-(imidazol-1-yl)ethanol, except that the hydroxyl hydrogen is replaced by a 4-chlorobenzyl group. It is an ether compound belonging to the imidazolium, dichlorobenzene, and monochlorobenzene classes. It is a broad-spectrum antifungal drug with some activity against Gram-positive bacteria. It can be used to treat dermatophyte infections and can be administered orally or by injection. Econazole is an azole antifungal drug. Econazole is an imidazolium compound with antifungal activity. Econazole disrupts the integrity of fungal cell walls by inhibiting 14α-demethylase, an enzyme that catalyzes the conversion of lanosterol to ergosterol, an important component of the fungal cell wall. Therefore, this drug increases cell permeability, leading to leakage of cell contents. In addition, econazole is also believed to inhibit endogenous respiration, interact with membrane phospholipids, inhibit purine absorption, and impair the biosynthesis of triglycerides and/or phospholipids. Econazole is only present in individuals who have used or taken the drug. It is a broad-spectrum antifungal agent with some activity against Gram-positive bacteria. It can be used topically to treat dermatophytes, or administered orally or by injection. [PubChem] Econazole interacts with 14α-demethylase, a cytochrome P-450 enzyme essential for the conversion of lanosterol to ergosterol. Since ergosterol is an important component of the fungal cell membrane, inhibition of its synthesis leads to increased cell permeability, resulting in leakage of cell contents. Econazole may also inhibit endogenous respiration, interact with membrane phospholipids, inhibit the transformation of yeast into mycelium, inhibit purine absorption, and impair the biosynthesis of triglycerides and/or phospholipids.
A commonly used topical antifungal agent—an imidazole derivative. See also: Econazole nitrate (in salt form); Econazole sulfosalicylate (its active ingredient).

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Indications
For the topical treatment of tinea pedis, tinea cruris, and tinea corporis caused by Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton capitis, Microsporum canis, Microsporum audouinii, Microsporum gypseum, and Epidermophyton floccosum, as well as cutaneous candidiasis and tinea versicolor.
FDA Label

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Mechanism of Action
Econazole interacts with 14α-demethylase, a cytochrome P-450 enzyme essential for the conversion of lanosterol to ergosterol. Since ergosterol is a crucial component of the fungal cell membrane, inhibition of its synthesis leads to increased cell permeability, resulting in leakage of cell contents. Econazole may also inhibit endogenous respiration, interact with membrane phospholipids, inhibit yeast conversion to mycelium, inhibit purine uptake, and impair the biosynthesis of triglycerides and/or phospholipids.

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Pharmacodynamics
Econazole is an antifungal drug, belonging to the same class as fluconazole (Diflucan), ketoconazole (Nizoral), itraconazole (Sporanox), and clotrimazole (Lotrimin, Mycelex). Econazole prevents fungi from producing key substances necessary for their growth and function. This drug is only effective against fungal infections. It is ineffective against bacterial or viral infections.

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- Econazole is an imidazole broad-spectrum antifungal drug[1]
- Its mechanism of action is to inhibit fungal lanosterol 14α-demethylase (a key enzyme in ergosterol biosynthesis), leading to ergosterol depletion and the accumulation of toxic sterol intermediates, thereby disrupting the integrity of the fungal cell membrane[1]
- Clinically, econazole is suitable for treating superficial fungal infections (such as tinea corporis, tinea pedis, and candidiasis) and has the potential to treat severe fungal infections[1]
- Econazole has no significant cross-resistance with other antifungal drugs and low cytotoxicity to mammalian cells[1]

C18H15CL3N2O

381.6835

380.024

27220-47-9

Econazole nitrate;24169-02-6

3198

White to off-white solid powder

1.3±0.1 g/cm3

533.8±50.0 °C at 760 mmHg

86.8ºC

276.6±30.1 °C

0.0±1.4 mmHg at 25°C

1.615

5.32

0

2

6

24

379

0

LEZWWPYKPKIXLL-UHFFFAOYSA-N

InChI=1S/C18H15Cl3N2O/c19-14-3-1-13(2-4-14)11-24-18(10-23-8-7-22-12-23)16-6-5-15(20)9-17(16)21/h1-9,12,18H,10-11H2

1-[2-[(4-chlorophenyl)methoxy]-2-(2,4-dichlorophenyl)ethyl]imidazole

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 : ~100 mg/mL (~262.00 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.55 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 25.0 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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 (Please use freshly prepared in vivo formulations for optimal results.)