Bifonazole ( Bifomyk; Bay H-4502; Bifokey;Bifon) is a potent imidazole-based antifungal drug with a broad-spectrum of antimycotic activity by interfering with sterol biosynthesis. Bifonazole has dual mode of action by blocking the transformation of 24-methylendihydrolanosterol to desmethylsterol in fungi together with inhibition of HMG-CoA. This enables fungicidal properties against dermatophytes and distinguishes bifonazole from other antifungal drugs. Bifonazole is a marketed drug developed by Bayer under the trade name of Canespor in ointment form.
Physicochemical Properties
| Molecular Formula | C22H18N2 |
| Molecular Weight | 310.3917 |
| Exact Mass | 310.147 |
| Elemental Analysis | C, 85.13; H, 5.85; N, 9.03 |
| CAS # | 60628-96-8 |
| PubChem CID | 2378 |
| Appearance | White to off-white solid powder |
| Density | 1.1±0.1 g/cm3 |
| Boiling Point | 491.7±24.0 °C at 760 mmHg |
| Melting Point | 142℃ |
| Flash Point | 251.2±22.9 °C |
| Vapour Pressure | 0.0±1.2 mmHg at 25°C |
| Index of Refraction | 1.616 |
| LogP | 4.84 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 1 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 24 |
| Complexity | 362 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | N1(C([H])=NC([H])=C1[H])C([H])(C1C([H])=C([H])C([H])=C([H])C=1[H])C1C([H])=C([H])C(C2C([H])=C([H])C([H])=C([H])C=2[H])=C([H])C=1[H] |
| InChi Key | OCAPBUJLXMYKEJ-UHFFFAOYSA-NOCAPBUJLXMYKEJ-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C22H18N2/c1-3-7-18(8-4-1)19-11-13-21(14-12-19)22(24-16-15-23-17-24)20-9-5-2-6-10-20/h1-17,22H |
| Chemical Name | 1-[Phenyl-(4-phenylphenyl)methyl]imidazole |
| Synonyms | Mycospor; Bay-H-4502; Bifokey; Amycor; Bay H-4502; Bifomyk; Bifonazol; Trifonazole; Bay H 4502; Bifon; Moldina |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| Targets | Antifungal |
| ln Vitro | Sterol biosynthesis is hampered by the new broad-spectrum antimycotic bifonazole (Bay H-4502). Bifonazole also directly inhibits HMG-CoA-reductase in dermatophytes. Bifonazole acts sequentially, inhibiting both direct inhibition of HMG-CoA-reductase and the cytochrome P450-dependent C14-demethylation of sterols. Bifonazole (Bay H-4502) exhibits a highly pH-dependent efficacy in vitro.Using various pathogens, the uptake kinetics of Bifonazole (Bay H-4502) have been measured[1]. In addition, compared to clotrimazole, bifonazole (Bay H-4502) generally causes a lower rate of sterol biosynthesis because it directly inhibits microsomal HMG-CoA-reductase. Bifonazole (Bay H-4502) is thought to have additional fungicidal effects that stem from sequential inhibition of cytochrome P450 and HMG-CoA-reductase. [2]. The choice of medium had an impact on bifonazole (Bay H-4502), with Kimmig's agar typically providing the lowest MICs. When tested on Kimmig's agar, it was found that the MICs of befonazole varied with pH (maximum activity at pH 6.5) with certain yeasts[3]. |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion Very low absorption following topical administration (0.6% of an applied dose). In cases of skin lesions absorption is increased (2.5%). Metabolism / Metabolites Hepatic. Biological Half-Life 1-2 hours |
| References |
[1]. Plempel, Bifonazole, a biochemist's view. Dermatologica, 1984. 169 Suppl 1: p. 3-9. [2]. Bifonazole and clotrimazole. Their mode of action and the possible reason for the fungicidal behaviour of bifonazole. Arzneimittelforschung, 1984. 34(2): p. 139-46. [3]. Shadomy, S., D.M. Dixon, and R. May, A comparison of bifonazole (BAY H 4502) with clotrimazole in vitro. Sabouraudia, 1982. 20(4): p. 313-23. |
| Additional Infomation |
1-[biphenyl-4-yl(phenyl)methyl]imidazole is a member of the class of imidazoles carrying an alpha-(biphenyl-4-yl)benzyl substituent at position 1. It is a member of imidazoles and a member of biphenyls. Bifonazole is an azole antifungal drug. Drug Indication Used for the treatment of various topical fungal infections, including athlete's foot (tinea pedis). Mechanism of Action Bifonazole works by inhibiting the production of a substance called ergosterol, which is an essential component of fungal cell membranes.It acts to destabilize the fungal cyctochrome p450 51 enzyme (also known as Lanosterol 14-alpha demethylase). This is vital in the cell membrance structure of the fungus. Its inhibition leads to cell lysis. The disruption in production of ergosterol disrupts the cell membrane and causes holes to appear. The cell membranes of fungi are vital for their survival. They keep unwanted substances from entering the cells and stop the contents of the cells from leaking out. As bifonazole causes holes to appear in the cell membranes, essential constituents of the fungal cells can leak out. This kills the fungi. Pharmacodynamics Bifonazole is a type of antifungal medicine known as an imidazole. It kills fungi and yeasts by interfering with their cell membranes. |
Solubility Data
| Solubility (In Vitro) |
DMSO : 33.33~62 mg/mL ( 107.38~199.74 mM ) Ethanol : ~20 mg/mL H2O :< 0.1 mg/mL |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.05 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: ≥ 2.5 mg/mL (8.05 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (8.05 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 2.5 mg/mL (8.05 mM) (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.2218 mL | 16.1088 mL | 32.2175 mL | |
| 5 mM | 0.6444 mL | 3.2218 mL | 6.4435 mL | |
| 10 mM | 0.3222 mL | 1.6109 mL | 3.2218 mL |