This article is missing information about biosynthesis pathway.(January 2022) |
Clinical data | |
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Trade names | Natacyn, others |
AHFS/Drugs.com | Monograph |
Routes of administration | Eye drops [1] |
ATC code | |
Identifiers | |
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CAS Number | |
PubChem CID | |
DrugBank | |
ChemSpider | |
UNII | |
KEGG | |
ChEMBL | |
E number | E235 (preservatives) |
CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.028.803 |
Chemical and physical data | |
Formula | C33H47NO13 |
Molar mass | 665.733 g·mol−1 |
3D model (JSmol) | |
Density | 1.35 g/ml g/cm3 |
Melting point | Darkens at ±200 °C with vigorous decomposition at 280-300 °C |
Solubility in water | 0.39 mg/ml |
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Natamycin, also known as pimaricin, is an antifungal medication used to treat fungal infections around the eye. [1] [2] This includes infections of the eyelids, conjunctiva, and cornea. [1] It is used as eyedrops. [1] Natamycin is also used in the food industry as a preservative. [2]
Allergic reactions may occur. [1] It is unclear if medical use during pregnancy or breastfeeding is safe. [1] It is in the macrolide and polyene families of medications. [1] It results in fungal death by altering the cell membrane. [1]
Natamycin was discovered in 1955 and approved for medical use in the United States in 1978. [1] [2] It is on the World Health Organization's List of Essential Medicines. [3] It is produced by fermentation of certain types of the bacterium Streptomyces . [1] [4]
Natamycin is used to treat fungal infections, including Candida , Aspergillus , Cephalosporium , Fusarium , and Penicillium . It is applied topically as a cream, in eye drops, or (for oral infections) in a lozenge. Natamycin shows negligible absorption into the body when administered in these ways. When taken orally, little or none is absorbed from the gastrointestinal tract, making it inappropriate for systemic infections. [5] Natamycin lozenges are used by veterinarians for oral thrush. [6]
Natamycin has been used for decades in the food industry as a hurdle to fungal outgrowth in dairy products and other foods. Potential advantages for the usage of natamycin might include the replacement of traditional chemical preservatives, a neutral flavor impact, and less dependence on pH for efficacy, as is common with chemical preservatives. It can be applied in a variety of ways: as an aqueous suspension (such as mixed into a brine) sprayed on the product or into which the product is dipped, or in powdered form (along with an anticaking agent such as cellulose) sprinkled on or mixed into the product.[ citation needed ]
Natamycin is approved for various dairy applications in the United States. More specifically, natamycin is commonly used in products such as cream cheeses, cottage cheese, sour cream, yogurt, shredded cheeses, cheese slices, and packaged salad mixes. One of the reasons for food producers to use natamycin is to replace the artificial preservative sorbic acid. [7] Natamycin is also known to diffuse slower and lesser into cheese when compared to sorbate, which could otherwise cause undesirable changes to the flavor. [8]
As a food additive, it has E number E235. Throughout the European Union, it is approved only as a surface preservative for certain cheese and dried sausage products. It must not be detectable 5 mm below the rind. While natamycin is approved in different applications at different levels in the world, it is approved in over 150 countries worldwide. [9]
While not currently approved for use on meats in the United States, some countries allow natamycin to be applied to the surface of dry and fermented sausages to prevent mold growth on the casing. Sausages that contain cheese, even in countries that don't allow its use on meats, may contain and list natamycin as an ingredient.
The European Food Safety Authority (EFSA) panel took over the responsibilities of providing scientific food safety advice to the EU from the Scientific Committee on Food in 2002. [10] In 2009, the EFSA considered the proposed use levels of natamycin are safe if it is used for the surface treatment for these cheese and sausage types. [11]
Natamycin does not have acute toxicity. In animal studies, the lowest LD50 found was 2.5-4.5 g/kg. [12] In rats, the LD50 is ≥2300 mg/kg, and doses of 500 mg/kg/day over two years caused no detectable differences in survival rate, growth, or incidence of tumors. The metabolites of natamycin also lack toxicity. The breakdown products of natamycin under various storage conditions may have a lower LD50 than natamycin, but in all cases, the numbers are quite high. In humans, a dose of 500 mg/kg/day repeated over multiple days caused nausea, vomiting, and diarrhea. [13]
No evidence shows natamycin, at either pharmacological levels or levels encountered as a food additive, can harm normal intestinal flora, but definitive research may not be available. [13] However, some people are allergic to natamycin. [14]
The EFSA has concluded that the use of natamycin as a food additive has no relevant risk for the development of resistant fungi. [11]
Natamycin inhibits the growth of fungi by specifically binding to ergosterol present in fungal cell membranes. Natamycin inhibits amino acid and glucose transport proteins leading to a loss of nutrient transport across the plasma membrane. While this binding is reversible, ergosterol binding acts as a universal mechanism of fungal inhibition, allowing natamycin to act on diverse fungal pathogens from Saccharomyces yeast to Aspergillus moulds. Natamycin is unique amongst related antifungals specifically because it does not directly cause membrane permeabilization. [15] [16] [17] Structurally-related antibiotics with similar binding properties are thought to produce hydrophilic channels that allow leakage of potassium and sodium ions from the cell. [18]
Natamycin has very low solubility in water; however, natamycin is effective at very low levels. Its minimum inhibitory concentration is less than 10 ppm for most molds.[ citation needed ]
Natamycin is produced as a secondary metabolite by some Streptomyces species: S. natalensis , S. lydicus , S. chattanoogensis and S. gilvosporeus . [4] Structurally, its core is a macrolide containing a polyene segment, with carboxylic acid and mycosamine groups attached. As with other polyene antimycotics, the biosynthesis begins with a series of polyketide synthase modules, followed by additional enzymatic processes for oxidation and attachment of the substituents. [19]
Natamycin is produced on an industrial scale by fermentation of various Streptomyces strains, including S. chattanoogensis L10. [19]
Natamycin was first isolated in 1955 from fermentation broth of a Streptomyces natalensis cell culture. [20] It was originally named pimaricin to honor Pietermaritzburg, where Streptomyces natalensis was acquired. Pimaricin was later renamed after the World Health Organization (WHO) mandated that antibiotics produced by Streptomyces end in –mycin. The name natamycin was chosen in reference to the natalensis species name. [20]
Natamycin appears on Whole Foods' "Unacceptable Ingredients for Food" list. [21]
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.
Nystatin, sold under the brand name Mycostatin among others, is an antifungal medication. It is used to treat Candida infections of the skin including diaper rash, thrush, esophageal candidiasis, and vaginal yeast infections. It may also be used to prevent candidiasis in those who are at high risk. Nystatin may be used by mouth, in the vagina, or applied to the skin.
Amphotericin B is an antifungal medication used for serious fungal infections and leishmaniasis. The fungal infections it is used to treat include mucormycosis, aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, and cryptococcosis. For certain infections it is given with flucytosine. It is typically given intravenously.
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.
An antimicrobial is an agent that kills microorganisms (microbicide) or stops their growth. Antimicrobial medicines can be grouped according to the microorganisms they act primarily against. For example, antibiotics are used against bacteria, and antifungals are used against fungi. They can also be classified according to their function. The use of antimicrobial medicines to treat infection is known as antimicrobial chemotherapy, while the use of antimicrobial medicines to prevent infection is known as antimicrobial prophylaxis.
Terbinafine is an antifungal medication used to treat pityriasis versicolor, fungal nail infections, and ringworm including jock itch and athlete's foot. It is either taken by mouth or applied to the skin as a cream or ointment. The cream and ointment should not be used for fungal nail infections.
In chemistry, an ionophore is a chemical species that reversibly binds ions. Many ionophores are lipid-soluble entities that transport ions across the cell membrane. Ionophores catalyze ion transport across hydrophobic membranes, such as liquid polymeric membranes or lipid bilayers found in the living cells or synthetic vesicles (liposomes). Structurally, an ionophore contains a hydrophilic center and a hydrophobic portion that interacts with the membrane.
Tiabendazole, also known as thiabendazole or TBZ and the trade names Mintezol, Tresaderm, and Arbotect, is a preservative, an antifungal agent, and an antiparasitic agent.
Polyene antimycotics, sometimes referred to as polyene antibiotics, are a class of antimicrobial polyene compounds that target fungi. These polyene antimycotics are typically obtained from certain species of Streptomyces bacteria. Previously, polyenes were thought to bind to ergosterol in the fungal cell membrane, weakening it and causing leakage of K+ and Na+ ions, which could contribute to fungal cell death. However, more detailed studies of polyene molecular properties have challenged this model suggesting that polyenes instead bind and extract ergosterol directly from the cellular membrane thus disrupting the many cellular functions ergosterols perform. Amphotericin B, nystatin, and natamycin are examples of polyene antimycotics. They are a subgroup of macrolides.
Lactobacillales are an order of gram-positive, low-GC, acid-tolerant, generally nonsporulating, nonrespiring, either rod-shaped (bacilli) or spherical (cocci) bacteria that share common metabolic and physiological characteristics. These bacteria, usually found in decomposing plants and milk products, produce lactic acid as the major metabolic end product of carbohydrate fermentation, giving them the common name lactic acid bacteria (LAB).
Butenafine, sold under the brand names Lotrimin Ultra, Mentax, and Butop, is a synthetic benzylamine derived antifungal drug.
Echinocandins are a class of antifungal drugs that inhibit the synthesis of β-glucan in the fungal cell wall via noncompetitive inhibition of the enzyme 1,3-β glucan synthase. The class has been dubbed the "penicillin of antifungals," along with the related papulacandins, as their mechanism of action resembles that of penicillin in bacteria. β-glucans are carbohydrate polymers that are cross-linked with other fungal cell wall components, the fungal equivalent to bacterial peptidoglycan. Caspofungin, micafungin, and anidulafungin are semisynthetic echinocandin derivatives with limited clinical use due to their solubility, antifungal spectrum, and pharmacokinetic properties.
Hamycin is a pair polyene antimycotic organic compounds described in India. It is a heptaene antifungal compound rather similar in chemical structure to amphotericin B except that it has an additional aromatic group bonded to the molecule. When pure, hamycin is a yellow, powdered solid. There are two versions of hamycin with very similar chemical structures: hamycin A and hamycin B.
Hachimycin, also known as trichomycin, is a polyene macrolide antibiotic, antiprotozoal, and antifungal derived from streptomyces. It was first described in 1950, and in most research cases have been used for gynecological infections.
Polylysine refers to several types of lysine homopolymers, which may differ from each other in terms of stereochemistry and link position (α/ε). Of these types, only ε-poly-L-lysine is produced naturally.
Clavams are a class of β-lactam antibiotics. These antibiotics are derived from Streptomyces clavuligerus NRRL 3585. This class is divided into the clavulanic acid class and the 5S clavams class. Both groups are the outcomes of the fermentation process produced by Streptomyces spp. Clavulanic acid is a broad-spectrum antibiotic and 5S clavams may have anti-fungal properties. They are similar to penams, but with an oxygen substituted for the sulfur. Thus, they are also known as oxapenams.
Streptomyces natalensis is a bacterial species in the genus Streptomyces.
Streptomyces isolates have yielded the majority of human, animal, and agricultural antibiotics, as well as a number of fundamental chemotherapy medicines. Streptomyces is the largest antibiotic-producing genus of Actinomycetota, producing chemotherapy, antibacterial, antifungal, antiparasitic drugs, and immunosuppressants. Streptomyces isolates are typically initiated with the aerial hyphal formation from the mycelium.
Streptomyces lydicus is a bacterium species from the genus of Streptomyces which has been isolated from soil in the United States. Streptomyces lydicus produces actithiazic acid, natamycin, lydimycin, streptolydigin, and 1-deoxygalactonojirimycin. Streptomyces lydicus can be used as an agent against fungal plant pathogens like Fusarium, Pythium, Phytophthora, Rhizoctonia and Verticillum.
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.
Natamycin was isolated for the first time in 1955 in the Gist-brocades research laboratories, from the fermentation broth of a culture of Streptomyces natalensis.