An antifungal medication, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as cryptococcal meningitis, and others. Such drugs are usually obtained by a doctor's prescription, but a few are available over the counter (OTC). The evolution of antifungal resistance is a growing threat to health globally.
Cytochromes P450 are a superfamily of enzymes containing heme as a cofactor that mostly, but not exclusively, function as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compounds, as well as for hormone synthesis and breakdown. In 1963, Estabrook, Cooper, and Rosenthal described the role of CYP as a catalyst in steroid hormone synthesis and drug metabolism. In plants, these proteins are important for the biosynthesis of defensive compounds, fatty acids, and hormones.
Ketoconazole, sold under the brand name Nizoral among others, is an antiandrogen, antifungal, and antiglucocorticoid medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin infections such as tinea, cutaneous candidiasis, pityriasis versicolor, dandruff, and seborrheic dermatitis. Taken by mouth it is a less preferred option and only recommended for severe infections when other agents cannot be used. Other uses include treatment of excessive male-patterned hair growth in women and Cushing's syndrome.
Fluconazole is an antifungal medication used for a number of fungal infections. This includes candidiasis, blastomycosis, coccidioidomycosis, cryptococcosis, histoplasmosis, dermatophytosis, and tinea versicolor. It is also used to prevent candidiasis in those who are at high risk such as following organ transplantation, low birth weight babies, and those with low blood neutrophil counts. It is given either by mouth or by injection into a vein.
Ergosterol (ergosta-5,7,22-trien-3β-ol) is a mycosterol found in cell membranes of fungi and protozoa, serving many of the same functions that cholesterol serves in animal cells. Because many fungi and protozoa cannot survive without ergosterol, the enzymes that synthesize it have become important targets for drug discovery. In human nutrition, ergosterol is a provitamin form of vitamin D2; exposure to ultraviolet (UV) light causes a chemical reaction that produces vitamin D2.
Miconazole, sold under the brand name Monistat among others, is an antifungal medication used to treat ring worm, pityriasis versicolor, and yeast infections of the skin or vagina. It is used for ring worm of the body, groin, and feet. It is applied to the skin or vagina as a cream or ointment.
Terconazole is an antifungal drug used to treat vaginal yeast infection. It comes as a lotion or a suppository and disrupts the biosynthesis of fats in a yeast cell. It has a relatively broad spectrum compared to azole compounds but not triazole compounds. Testing shows that it is a suitable compound for prophylaxis for those that suffer from chronic vulvovaginal candidiasis.
Any enzyme system that includes cytochrome P450 protein or domain can be called a P450-containing system.
Posaconazole, sold under the brand name Noxafil among others, is a triazole antifungal medication.
Lanosterol 14α-demethylase (CYP51A1) is the animal version of a cytochrome P450 enzyme that is involved in the conversion of lanosterol to 4,4-dimethylcholesta-8(9),14,24-trien-3β-ol. The cytochrome P450 isoenzymes are a conserved group of proteins that serve as key players in the metabolism of organic substances and the biosynthesis of important steroids, lipids, and vitamins in eukaryotes. As a member of this family, lanosterol 14α-demethylase is responsible for an essential step in the biosynthesis of sterols. In particular, this protein catalyzes the removal of the C-14α-methyl group from lanosterol. This demethylation step is regarded as the initial checkpoint in the transformation of lanosterol to other sterols that are widely used within the cell.
Progesterone receptor membrane component 1 is a protein which co-purifies with progesterone binding proteins in the liver and ovary. In humans, the PGRMC1 protein is encoded by the PGRMC1 gene.
Clotrimazole, sold under the brand name Lotrimin, among others, is an antifungal medication. It is used to treat vaginal yeast infections, oral thrush, diaper rash, tinea versicolor, and types of ringworm including athlete's foot and jock itch. It can be taken by mouth or applied as a cream to the skin or in the vagina.
C-5 sterol desaturase is an enzyme that is highly conserved among eukaryotes and catalyzes the dehydrogenation of a C-5(6) bond in a sterol intermediate compound as a step in the biosynthesis of major sterols. The precise structure of the enzyme's substrate varies by species. For example, the human C-5 sterol desaturase oxidizes lathosterol, while its ortholog ERG3 in the yeast Saccharomyces cerevisiae oxidizes episterol.
Prochloraz, brand name Sportak, is an imidazole fungicide that was introduced in 1978 and is widely used in Europe, Australia, Asia, and South America within gardening and agriculture to control the growth of fungi. It is not registered for use in the United States. Similarly to other azole fungicides, prochloraz is an inhibitor of the enzyme lanosterol 14α-demethylase (CYP51A1), which is necessary for the production of ergosterol – an essential component of the fungal cell membrane – from lanosterol. The agent is a broad-spectrum, protective and curative fungicide, effective against Alternaria spp., Botrytis spp., Erysiphe spp., Helminthosporium spp., Fusarium spp., Pseudocerosporella spp., Pyrenophora spp., Rhynchosporium spp., and Septoria spp.
ERG11 or Sterol 14-demethylase is a fungal cytochrome P450 enzyme originally from Saccharomyces cerevisiae, belongs to family CYP51, with the CYP Symbol CYP51F1. ERG11 catalyzes the C14-demethylation of lanosterol to 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol which is the first step of biosynthesis of the zymosterol, zymosterol will be further converted into Ergosterol.
Dihydrolanosterol, or 24,25-Dihydrolanosterol, also called Lanostenol, is a sterol and the C24-25 hydrogenated products of lanosterol, dihydrolanosterol can be demethylated by mammal or yeast cytochrome P450 sterol 14alpha-demethylase.
Eburicol, or Obtusifoldienol, also called 24-Methylene-24,25-dihydrolanosterol, is a natural, fungus sterol, which can be demethylated by yeast cytochrome P450 sterol 14alpha-demethylase ERG11.
ERG5 or Sterol 22-desaturase is a cytochrome P450 enzyme in the ergosterol biosynthesis pathway of fungi Saccharomyces cerevisiae, with the CYP Symbol CYP61A1. CYP61A1 is one of only three P450 enzyme found in baker's yeast, the other two are CYP51F1 and CYP56A1. The ortholog in Schizosaccharomyces pombe, was named CYP61A3 for historical reasons, and is only one of two P450 enzyme found with CYP51F1. ERG5 catalyzes the C22-C23 double bond formation on the sterol side chain of ergostatrienol to convert it into ergostatetraenol, then the C24 double bond of ergostatetrenol will be hydrogenation reduced into ergosterol by ERG4.
29-Norlanosterol, or 4-demethyllanosterol, also called 4α,14α-dimethylzymosterol, is a Metabolic intermediate of plant sterol biosynthesis. In the pathway, it is transformed from ring-opening reactions of Norcycloartenol and then demethylation by CYP51 into 4α-methyl-5α-cholesta-8,14,24-trien-3β-ol.
Topical antifungaldrugs are used to treat fungal infections on the skin, scalp, nails, vagina or inside the mouth. These medications come as creams, gels, lotions, ointments, powders, shampoos, tinctures and sprays. Most antifungal drugs induce fungal cell death by destroying the cell wall of the fungus. These drugs inhibit the production of ergosterol, which is a fundamental component of the fungal cell membrane and wall.
