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| Other Sizes |
| Targets |
Miconazole primarily targets 14α-sterol demethylase (CYP51), a cytochrome P450 enzyme found exclusively in fungi. By inhibiting this enzyme, miconazole prevents the conversion of lanosterol to ergosterol. The resulting decrease in ergosterol production leads to altered cell membrane composition and permeability, which in turn causes leakage of cations, phosphate, and low molecular weight proteins. The accumulation of toxic methylated sterol precursors further contributes to fungal cell death. Miconazole also inhibits aromatase (CYP19), which may contribute to additional biological effects. Unique among the azoles, miconazole is thought to act through three main mechanisms.
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| ln Vitro |
Miconazole is a topical imidazole antifungal medication that was created by Janssen Pharmaceutica to treat fungal infections of the skin or mucous membranes. Ergosterol is a crucial component of fungal cell membranes, and it functions by preventing its formation. Additionally, it is utilized to combat some species of Leishmania, a single-celled parasite whose cell membrane also contains ergosterol. It also possesses certain antibacterial qualities in addition to its antifungal and antiparasitic actions. Miconazole is also utilized as a formaldehyde substitute in the development of Ektachrome film during the Kodak E-6 process' final processing, as well as in the comparable Fuji CR-56 process. In the composition of its C-41RA Quick Access color negative developing process, Fuji Hunt also incorporates Miconazole as a final rinse ingredient.
In vitro, miconazole has demonstrated potent antifungal activity against a wide range of fungi. The compound inhibits ergosterol synthesis by targeting 14α-sterol demethylase, leading to increased cellular permeability and leakage of cellular contents. Miconazole shows activity against Candida species, dermatophytes, and other pathogenic fungi. It also has some activity against Gram-positive bacteria. The compound's inhibition of aromatase (CYP19) has been characterized in biochemical assays. Miconazole has been shown to promote remyelination in vitro in oligodendrocyte precursor cell models. Its antifungal activity is concentration-dependent, with MIC values varying depending on the fungal species. |
| ln Vivo |
In vivo, miconazole is used clinically for the treatment of candidal skin infections and yeast infections of the skin or vagina. It is available in various topical formulations including creams, powders, and suppositories. Miconazole has been shown to promote remyelination of neurons in chronic progressive multiple sclerosis mouse models, suggesting potential applications beyond antifungal therapy. Its antifungal efficacy has been demonstrated in various animal models of fungal infection. The compound's safety and efficacy in humans have been established through clinical use. Miconazole is also used in research to study cholesterol synthesis and fungal membrane biology.
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| Enzyme Assay |
For in vitro biochemical assays, miconazole is evaluated for its antifungal activity and enzyme inhibition. Ergosterol synthesis inhibition is assessed by measuring ergosterol levels in fungal cultures using HPLC or spectrophotometric methods. 14α-demethylase activity is measured using enzyme assays with appropriate substrates. Aromatase (CYP19) inhibition is assessed using enzyme activity assays. Minimum inhibitory concentration (MIC) is determined using broth microdilution or agar dilution methods against various fungal species. Fungal membrane permeability is assessed by measuring leakage of cellular contents. These cell-free and cell-based assays help characterize the compound's antifungal activity and mechanism of action.
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| Cell Assay |
In vitro cellular assays for miconazole are performed using fungal cultures and mammalian cell lines. Fungi including Candida species and dermatophytes are cultured in appropriate media and treated with miconazole at various concentrations. Fungal growth is monitored by measuring optical density, colony counts, or metabolic activity. Ergosterol content is measured by extraction and HPLC analysis. Membrane permeability is assessed by measuring leakage of intracellular contents. In mammalian cells, effects on cholesterol synthesis and aromatase activity can be assessed. Oligodendrocyte precursor cell cultures are used to study remyelination-promoting effects. Cytotoxicity is assessed using MTT or LDH release assays. These cellular assays help validate the compound's antifungal and other biological activities.
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| Animal Protocol |
In vivo animal experiments with miconazole are conducted to study its antifungal efficacy and other biological effects. Animal models of fungal infection, including cutaneous and vaginal candidiasis, are commonly used. Miconazole is applied topically or administered systemically. Efficacy endpoints include fungal load reduction, resolution of infection symptoms, and tissue histopathology. For multiple sclerosis research, mouse models of chronic progressive multiple sclerosis are used to study remyelination-promoting effects. Miconazole is administered orally or intraperitoneally, and remyelination is assessed by histological analysis and functional tests. The compound's safety and tolerability are monitored through body weight, clinical signs, and clinical chemistry.
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| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
Following a single oral dose of 50 mg miconazole tablets in healthy volunteers, the mean Cmax was 15.1 ± 16.2 mcg/mL, the mean AUC0-24 was 55.2 ± 35.1 mcgh/mL, and the median Tmax was 7 hours (range 2.0–24.1 hours). Measurable plasma concentrations in these patients ranged from 0.5 to 0.83 mcg/mL. Topically applied miconazole showed poor absorption into the systemic circulation. In pediatric patients aged 1–21 months, after multiple topical applications of miconazole ointment over 7 consecutive days, 88% of patients had plasma miconazole concentrations below 0.5 ng/mL, while the remaining patients had concentrations of 0.57 ng/mL and 0.58 ng/mL, respectively. Similarly, [the text abruptly ends here, likely due to an incomplete sentence or missing information]. Following administration of a 1200 mg vaginal suppository, the mean Cmax was 10.71 ng/mL, the mean Tmax was 18.4 hours, and the mean AUC0-96 was 477.3 ngh/mL. Miconazole is primarily excreted via urine and feces; less than 1% of unmetabolized miconazole is recovered in urine. The calculated apparent volume of distribution (VOD) of the 1200 mg miconazole vaginal suppository is 95,546 L, while that of the 100 mg vaginal cream is 10,911 L. Metabolites/Metabolites: Miconazole is metabolized in the liver without producing any active metabolites. Biological Half-Life: The terminal half-life of miconazole is 24 hours. Pharmacokinetic properties of miconazole have been characterized through clinical use. When applied topically, the compound has minimal systemic absorption. After oral administration, miconazole is absorbed from the gastrointestinal tract and distributed to tissues. It is metabolized in the liver by cytochrome P450 enzymes and eliminated primarily in feces. The compound has a half-life of approximately 20-24 hours. Protein binding is high (>90%). Miconazole is a known inhibitor of CYP3A4 and CYP2C9, leading to potential drug-drug interactions. Its pharmacokinetic properties support its use in topical and oral formulations. Detailed PK parameters are available in the pharmacological literature. |
| Toxicity/Toxicokinetics |
Toxicity Summary
Miconazole 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. Miconazole 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. Toxicity Data LD50: 3800 mg/kg (oral, mouse) (A308) LD50: 3 g/kg (oral, rat) (A308) The toxicological profile of miconazole has been characterized through extensive clinical use. Topical application is generally well-tolerated, with local irritation being the most common adverse effect. Oral administration can cause gastrointestinal disturbances, nausea, and vomiting. Hepatotoxicity has been reported rarely. Miconazole is contraindicated in patients with hypersensitivity to azole antifungals. It should be used with caution in patients with liver disease and in those taking medications metabolized by CYP3A4 or CYP2C9 due to drug interaction potential. The compound's safety in pregnancy and lactation has been established for topical use. Comprehensive toxicity studies have been conducted to support clinical use. |
| References | |
| Additional Infomation |
Pharmacodynamics
Miconazole is an azole antifungal drug whose main mechanism of action is by inhibiting specific demethylases in the CYP450 complex. Because miconazole is usually applied topically and is minimally absorbed into the systemic circulation after administration, most adverse reactions in patients are limited to hypersensitivity reactions and anaphylactic shock. Patients using vaginal miconazole preparations are advised not to rely on contraception to prevent pregnancy and sexually transmitted infections, and should not use tampons concurrently. Miconazole is a clinically approved antifungal agent with a long history of safe and effective use. Its broad-spectrum antifungal activity makes it valuable for treating various fungal infections. The compound's mechanism of action through ergosterol synthesis inhibition has been extensively studied and validated. Miconazole's inhibition of aromatase and its potential for promoting remyelination represent areas of ongoing research interest. The compound is used as a reference standard in antifungal susceptibility testing and in studies of fungal membrane biology. Its imidazole structure makes it a model compound for studying azole antifungals. Miconazole is also relevant for drug interaction studies due to its CYP450 inhibitory effects. |
| Molecular Formula |
C18H14CL4N2O
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|---|---|
| Molecular Weight |
416.13
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| Exact Mass |
413.986
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| CAS # |
22916-47-8
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| Related CAS # |
Miconazole nitrate;22832-87-7;Miconazole-d5;1216653-50-7;Miconazole-d5 nitrate;1216653-51-8;Miconazole-d2;2140316-33-0
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| PubChem CID |
4189
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
555.1±50.0 °C at 760 mmHg
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| Melting Point |
159-163ºC
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| Flash Point |
289.5±30.1 °C
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| Vapour Pressure |
0.0±1.4 mmHg at 25°C
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| Index of Refraction |
1.625
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| LogP |
5.93
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
25
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| Complexity |
417
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
BYBLEWFAAKGYCD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H14Cl4N2O/c19-13-2-1-12(16(21)7-13)10-25-18(9-24-6-5-23-11-24)15-4-3-14(20)8-17(15)22/h1-8,11,18H,9-10H2
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| Chemical Name |
1-[2-(2,4-dichlorophenyl)-2-[(2,4-dichlorophenyl)methoxy]ethyl]imidazole
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : 100 mg/mL (240.31 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.01 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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL 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. Solubility in Formulation 2: 2.08 mg/mL (5.00 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (5.00 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4031 mL | 12.0155 mL | 24.0310 mL | |
| 5 mM | 0.4806 mL | 2.4031 mL | 4.8062 mL | |
| 10 mM | 0.2403 mL | 1.2015 mL | 2.4031 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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