The primary target of Butoconazole is lanosterol 14α-demethylase (CYP51), an enzyme involved in ergosterol biosynthesis in fungi. By inhibiting this enzyme, butoconazole prevents the synthesis of ergosterol, a key component of the fungal cell membrane. This changes the fungal cell membrane lipid composition, alters cell permeability, and leads to growth inhibition.

In general, imidazole prevents lanosterol from being converted to ergosterol, which alters the lipid composition of fungal cell membranes. The osmotic death or growth inhibition of fungal cells is the final result of this structural alteration, which also modifies cell permeability [1].
In vitro, Butoconazole has been shown to have antifungal activity against Candida species, including C. albicans and C. tropicalis. It completely inhibits growth of a variety of fungi in vitro when used at concentrations of 0.05-30 µg/ml. The compound's fungistatic activity has been confirmed in various in vitro models.

In vivo, Butoconazole is used locally in the treatment of vulvovaginal candidiasis. It is effective for women who prefer solid-type vaginal preparations. The compound is similar in effectiveness to miconazole and clotrimazole.

In vitro enzyme or receptor binding assays for Butoconazole involve measuring its inhibition of lanosterol 14α-demethylase (CYP51) activity. The assay uses a purified fungal CYP51 enzyme and a substrate, such as lanosterol. The production of ergosterol is measured using chromatographic methods. The compound is incubated with the enzyme and substrate at varying concentrations to determine the IC50.

In vitro cell-based assays for Butoconazole are performed using fungal cultures, particularly Candida species. The fungus is grown in the presence of the compound, and the minimum inhibitory concentration (MIC) is determined. The compound's effects on fungal cell membrane composition and growth are assessed.

In vivo animal experiments for Butoconazole are conducted using animal models of vulvovaginal candidiasis. The compound is administered intravaginally, and its efficacy is evaluated by measuring the reduction in fungal load and improvement in clinical symptoms.

Absorption, Distribution and Excretion
Following intravaginal application of butoconazole nitrate vaginal cream, 2% to 3% of women absorbed an average of 1.7% (range 1.3–2.2%) of the dose.
Pharmacokinetic (PK) properties of Butoconazole indicate that it has a molecular weight of 474.79 and a molecular formula of C19H17Cl3N2S.HNO3. The CAS number is 64872-76-0. The IUPAC name is 1-[4-(4-chlorophenyl)-2-(2,6-dichlorophenyl)sulfanylbutyl]imidazole;nitric acid. It is a synthetic imidazole analog.

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
The use of butoconazole vaginally during lactation has not been studied. The absorption rate of vaginal doses is approximately 5.5%, and the plasma half-life is 21 to 24 hours. Since there is no published experience with butoconazole use during lactation, it is recommended to prioritize other medications, especially when breastfeeding newborns or preterm infants.
◉ Effects on Breastfed Infants
No relevant published information was found as of the revision date.
◉ Effects on Lactation and Breast Milk
No relevant published information was found as of the revision date.
Toxicology (toxicology) data for Butoconazole indicate that it is generally well-tolerated when used locally. Common side effects may include local irritation, burning, and itching. The compound is for topical use only and should not be ingested.

[1]. Anik ST, et al. Extreme vertexes design in formulation development: solubility of butoconazole nitrate in a multicomponent system. J Pharm Sci. 1981;70(8):897-900.
[2]. Pharmacology refers to the chemical makeup and behavior of GYNAZOLE 1 (butoconazole nitrate cream).

Butconazole belongs to the imidazole class of compounds, with the structure 1H-imidazolium, where the hydrogen atom bonded to the nitrogen atom is replaced by 4-(4-chlorophenyl)-2-[(2,6-dichlorophenyl)thio]butyl. It is an antifungal drug used in gynecology as a nitrate to treat vulvovaginal infections caused by Candida species, especially Candida albicans. It belongs to the imidazole, aryl sulfide, dichlorobenzene, monochlorobenzene, imidazole antifungal drugs, and conconazole antifungal drugs. It is the conjugate base of butconazole (1+). Butconazole is an imidazole antifungal drug used in gynecology. Butconazole is an azole antifungal drug. Butconazole is a synthetic imidazole derivative with antibacterial activity. Butconazole interferes with sterol biosynthesis by inhibiting the conversion of lanosterol to ergosterol, thereby altering the lipid composition of fungal cell membranes. This alters cell permeability and leads to growth inhibition. Butconazole nitrate is effective against a variety of dermatophytes and yeasts. It also has antibacterial activity against certain Gram-positive bacteria.
See also: Butonazole nitrate (in salt form).
Drug Indications
For the topical treatment of vulvovaginal candidiasis (infection caused by Candida).
FDA Label
Mechanism of Action
The exact mechanism of action of butonazole is not fully understood, but it is presumed to be similar to other imidazole derivatives, acting by inhibiting sterol synthesis. Imidazole drugs typically inhibit the conversion of lanosterol to ergosterol by inhibiting cytochrome P450 14α-demethylase, thereby altering the lipid composition of the fungal cell membrane. This structural change alters cell permeability, ultimately leading to osmotic disruption or growth inhibition of fungal cells.
Pharmacodynamics
Butonazole is an imidazole derivative with in vitro bactericidal activity against Candida species and has been shown to be clinically effective against vaginal infections caused by Candida albicans. Candida albicans has been identified as the main species causing vulvovaginal candidiasis.
Other information: Butoconazole is also known as RS 35887. It is a synthetic imidazole antifungal agent used for the treatment of vulvovaginal candidiasis. The compound is marketed under brand names such as Femstat and Gynomyk. Its CAS number is 64872-76-0.

C19H17CL3N2S

411.76

410.017

64872-76-0

Butoconazole nitrate;64872-77-1

47472

White to off-white solid powder

1.3±0.1 g/cm3

566.9±50.0 °C at 760 mmHg

68-70.5ºC

296.7±30.1 °C

0.0±1.5 mmHg at 25°C

1.634

6.88

0

2

7

25

383

0

SWLMUYACZKCSHZ-UHFFFAOYSA-N

InChI=1S/C19H17Cl3N2S/c20-15-7-4-14(5-8-15)6-9-16(12-24-11-10-23-13-24)25-19-17(21)2-1-3-18(19)22/h1-5,7-8,10-11,13,16H,6,9,12H2

1-(4-(4-chlorophenyl)-2-((2,6-dichlorophenyl)thio)butyl)-1H-imidazole

RS 35887-10-3 RS-35887-10-3 RS35887-10-3

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)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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