7681-93-8 Usage
Description
Pimaricin, also known as natamycin, is a naturally occurring macrolide polyene antifungal agent produced through the fermentation of the bacterium Streptomyces natalensis. It is characterized by a macrocyclic lactone ring with a number of conjugated carbon-carbon double bonds and has a low solubility in water. Pimaricin exhibits broad-spectrum antifungal activity by binding specifically to ergosterol in the cell membranes of fungi, disrupting the cell membrane and increasing cell permeability, ultimately leading to cell death.
Uses
Used in Medical Field:
Pimaricin is used as an antifungal agent for the treatment of various fungal infections caused by Candida, Aspergillus, Cephalosporium, Fusarium, and Penicillium. It is particularly used for the treatment of fungal keratitis, a type of eye infection.
Used in Food Industry Cheese Preservation:
Pimaricin is used as a natural preservative for surface treatment of cheeses, such as hard cheese and salamitype sausages, to prevent fungal outgrowth. It is tasteless, odorless, colorless, and does not penetrate the cheese, thus not affecting the ripening and flavor improvement process. It can be applied by spraying, dipping, or incorporating it into cheese coatings.
Used in Food Industry Surface Applications:
Pimaricin is used for surface applications on various food products to prevent fungal growth. It is effective against almost all foodborne yeasts and molds but has no effect on bacteria or viruses.
Used in Agriculture Disease Control:
Pimaricin is used for the control of diseases of bulbs, such as those caused by fungal infections.
Used in Pharmaceutical Industry Analgesic and Antimigraine:
Pimaricin has been reported to have potential uses as an analgesic and antimigraine agent, although further research may be required to fully understand its applications in this field.
References
https://en.wikipedia.org/wiki/Natamycin
https://www.drugbank.ca/drugs/DB00826
References
1) te Welscher?et al. (2008), Natamycin blocks fungal growth by binding specifically to ergosterol without permeabilizing the membrane; J. Biol. Chem.,?283?6393
2) te Welscheri?et al. (2012),?Polyene antibiotic that inhibits membrane transport proteins; Proc. Natl. Acad. Sci. USA.,?109?11156
3) te Welscher?et al. (2010),?Natamycin inhibits vacuole fusion at the priming phase via a specific interaction with ergosterol; Antimicrob. Agents Chemother.,?54?2618
Originator
Pimafucine,Beytout,France,1964
Manufacturing Process
The Fermentation Process: The process by which this antifungal substance is
produced is an aerobic fermentation of an aqueous nutrient medium The Fermentation Process: The process by which this antifungal substance is
produced is an aerobic fermentation of an aqueous nutrient medium.In more detail the nutrient medium used may contain sources of carbon such
as starch, hydrolyzed starch, sugars such as lactose, maltose, dextrose,
sucrose, or sugar sources such as molasses; alcohols, such as glycerol and
mannitol; organic acids, such as citric acid and acetic acid; and various
natural products which may contain other nutrient materials in addition to
carbonaceous substances.Nitrogen sources include proteins, such as casein, zein, lactalbumin; protein
hydrolyzates such proteoses, peptones, peptides, and commercially available
materials, such as N-Z Amine which is understood to be a casein hydrolyzate;
also corn steep liquor, soybean meal, gluten, cottonseed meal, fish meal,
meat extracts, stick liquor, liver cake, yeast extracts and distillers' solubles;
amino acids, urea, ammonium and nitrate salts. Such inorganic elements as
sodium, potassium, calcium and magnesium; and chlorides, sulfates,
phosphates and combinations of these anions and cations in the form of
mineral salts may be advantageously used in the fermentation.The so-called trace elements, such as boron, cobalt, iron, copper, zinc,
manganese, chromium, molybdenum and still others may also be used to
advantage. Generally, these trace elements occur in sufficient quantities in the
carbonaceous and nitrogenous constituents of the medium, particularly if
derived from natural sources, or in the tap water, and the addition of further
quantities of these trace elements may consequently be unnecessary.The fermentation liquor is aerated in the customary manner by forcing sterile
air through the fermenting mixture usually at the rate of about 1 volume of
air per volume of fermentation medium per minute. To minimize
contamination with foreign microorganisms, the fermentation vessels should
be closed and a pressure of 2 to 15 pounds above atmospheric pressure
maintained in the vessel. In addition to the agitation provided by aeration,
mechanical agitation is generally desirable. Antifoaming agents, such as 1%
octadecanol in lard oil, may be added from time to time as required to
prevent excessive foaming. Fermentation is conducted at a temperature
preferably on the order of 26°C to 30°C but may be as low as 17°C or as high
as 42°C.The time required for maximum production of the antifungal substance will
vary considerably depending upon other conditions of the fermentation.
Generally, about 48 hours is required before appreciable quantities of the
antifungal substance are detected in the medium. The production of the
antifungal substance increases with time, and the fermentation may run as
long as 120 hours. The hydrogen ion conditions normally vary from about pH
6 to pH 8.0, although deviations from these values are permissible, according
to British Patent 846,933. The reader is referred to the patents cited for detals
of pimaricin purification.
Therapeutic Function
Antibacterial (ophthalmic)
Biological Functions
Natamycin, also known as pimaracin, belongs to the polyene family of antibiotics; (a group of antifungal agents which target and bind to eukaryotic sterols and specifically ergosterol), and it is a secondary metabolite of Streptomyces natalensis . Very low levels (10–20 ppm) are needed to inhibit almost all yeasts and molds, while no amount of natamycin is sufficient to inhibit most bacteria, as they lack the sterol targeted by natamycin (some gram-positive types may be susceptible). Thus, natamycin may be used to retard the growth of fungi in meat products to which fermentative cultures are added, and is typically applied as a surface treatment (i.e., dip or spray). Resistant organisms are not typically encountered even though natamycin has been used as a food preservative for more than three decades. Unlike most bacteriocins, natamycin is toxic to eukaryotes. Acceptable daily intake of natamycin for humans is 0–0.3 mg/kg of body weight.
Antimicrobial activity
The spectrum of Natamycin's activity is somewhat narrower than that of amphotericin and nystatin,
but at the same time, it is less toxic. It exhibits especially pronounced activity against a few
strains of Fusarium and Cefalosporium. Natamycin is a drug for treating superficial fungal infections, and it is used only for ophthalmologic purposes. Synonyms of this drug are
pimafucin, pimaricin, tennecetin, and others.
Safety Profile
Poison by intravenous,
intramuscular, subcutaneous, and
intraperitoneal routes. Moderately toxic by
ingestion. When heated to decomposition it emits toxic fumes of NOx. Used as an
antibacterial agent.
Synthesis
Natamycin, a mixture of stereoisomeric 22-[(3-amino-3,6-dideoxy-β-Dmannopyranosyl)oxy]-1,3,26-trihydroxy-12-methyl-10-oxo-6,11,28-trioxatricyclo[22.3.1.0.5,7]-octacosa-8,14,16,18,20,penten-25-carboxylic acid (35.1.3), like amphotericin
and nystatin, is a polyene antibiotic that is isolated from the products of the vital activity of
the actinomycete Streptomyces natalensis.
Veterinary Drugs and Treatments
Natamycin is a semisynthetic polyene antibiotic. Natamycin is
poorly water-soluble and will not penetrate the intact corneal epithelium.
Natamycin is the only antifungal agent approved for use
on the eye and the only commercially available eye drug for treatment
of fungal keratitis.
Check Digit Verification of cas no
The CAS Registry Mumber 7681-93-8 includes 7 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 4 digits, 7,6,8 and 1 respectively; the second part has 2 digits, 9 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 7681-93:
(6*7)+(5*6)+(4*8)+(3*1)+(2*9)+(1*3)=128
128 % 10 = 8
So 7681-93-8 is a valid CAS Registry Number.
InChI:InChI=1/C33H47NO13/c1-18-10-8-6-4-3-5-7-9-11-21(45-32-30(39)28(34)29(38)19(2)44-32)15-25-27(31(40)41)22(36)17-33(42,47-25)16-20(35)14-24-23(46-24)12-13-26(37)43-18/h3-9,11-13,18-25,27-30,32,35-36,38-39,42H,10,14-17,34H2,1-2H3,(H,40,41)/b4-3+,7-5+,8-6-,11-9+,13-12+/t18-,19-,20+,21+,22+,23-,24-,25+,27-,28+,29-,30+,32?,33-/m1/s1
7681-93-8Relevant articles and documents
Structure of cytochrome P450 PimD suggests epoxidation of the polyene macrolide pimaricin occurs via a hydroperoxoferric intermediate
Kells, Petrea M.,Ouellet, Hugues,Santos-Aberturas, Javier,Aparicio, Jesus F.,Podust, Larissa M.
, p. 841 - 851 (2010)
We present the X-ray structure of PimD, both substrate-free and in complex with 4,5-desepoxypimaricin. PimD is a cytochrome P450 monooxygenase with native epoxidase activity that is critical in the biosynthesis of the polyene macrolide antibiotic pimaricin. Intervention in this secondary metabolic pathway could advance the development of drugs with improved pharmacologic properties. Epoxidation by P450 typically includes formation of a charge-transfer complex between an oxoferryl π-cation radical species (Compound I) and the olefin π-bond as the initial intermediate. Catalytic and structural evidence presented here suggest that epoxidation of 4,5-desepoxypimaricin proceeds via a hydroperoxoferric intermediate (Compound 0). The oxygen atom of Compound 0 distal to the heme iron may insert into the double bond of the substrate to make an epoxide ring. Stereoelectronic features of the putative transition state suggest substrate-assisted proton delivery.
POLYENE ANTIBIOTICS, COMPOSITIONS CONTAINING SAID ANTIBIOTICS, METHOD AND MICRO-ORGANISMS USED TO OBTAIN SAME AND APPLICATIONS THEREOF
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Page/Page column 5; 24; 29, (2008/06/13)
Abstract: The invention relates to novel polyenes having formula (I), wherein: R1 represents alkyl C1-C3; and R2 represents a functional group selected from CH3- or CONH2- (methyl- or primary amide-). The aforementioned polyenes have a biocide action on organisms comprising cell membranes that contain ergosterol, e.g., fungi or parasites. Said compounds can be obtained using a method that consists in cultivating a producing micro-organism under conditions that enable the production thereof. In addition, the invention also relates to a mechanism for the in vitro production of amidated polyenes, consisting in incubating carboxylated polyenes with cell-free extracts (or proteinaceous fractions) of the producers of same in the presence of ATP/Mg++ and an amide-group donor compound (preferably glutamine).
Pyrazolyl benzyl ether derivatives containing a fluoromethoxyimino group and use thereof as pesticides
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, (2008/06/13)
The invention relates to novel pyrazolyl benzyl ethers, to a plurality of processes for their preparation and to their use for controlling harmful organisms.
