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Identification
NameNatamycin
Accession NumberDB00826  (APRD01136)
Typesmall molecule
Groupsapproved
Description

Amphoteric macrolide antifungal antibiotic from Streptomyces natalensis or S. chattanoogensis. It is used for a variety of fungal infections, mainly topically. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
NatamicinaSpanishINN
NatamycinGermanINN
NatamycineFrenchINN
NatamycinumLatinINN
PimaricinNot AvailableJAN
SaltsNot Available
Brand names
NameCompany
FukricinSanbe
InfectoMykInfectopharm
N-MycinAristopharma
NatacynAlcon
NatadropsCipla
NatametSun
NatamycynaUnia
NatezhenAlcon
NatophIbn Sina
NatopticFDC
OptinatJayson
PimafucinAstellas
PimafusinElder
PimaricinSenju Seiyaku
Brand mixtures
Brand NameIngredients
Pimafucort Natamycin and Neomycin, Hydrocortisone
Categories
CAS number7681-93-8
WeightAverage: 665.7252
Monoisotopic: 665.304740595
Chemical FormulaC33H47NO13
InChI KeyNCXMLFZGDNKEPB-BQGNJOPGSA-N
InChI
InChI=1S/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
IUPAC Name
(1R,3S,5R,7R,12R,22R,24S,25R,26S)-22-{[(3S,4S,5S,6R)-4-amino-3,5-dihydroxy-6-methyloxan-2-yl]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-pentaene-25-carboxylic acid
SMILES
C[C@H]1OC(O[C@@H]2C[C@@H]3O[C@@](O)(C[C@H](O)[C@H]3C(O)=O)C[C@@H](O)C[C@H]3O[C@@H]3\C=C\C(=O)O[C@H](C)C\C=C\C=C\C=C\C=C\2)[C@@H](O)[C@@H](N)[C@@H]1O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassPhenylpropanoids and Polyketides
ClassMacrolides and Analogues
SubclassNot Available
Direct parentMacrolides and Analogues
Alternative parentsO-glycosyl Compounds; Hexoses; Amino Sugars; Beta Hydroxy Acids and Derivatives; Dicarboxylic Acids and Derivatives; Oxanes; Secondary Alcohols; Hemiacetals; Polyols; Carboxylic Acid Esters; 1,2-Aminoalcohols; Carboxylic Acids; Enolates; Acetals; Polyamines; Epoxides; Monoalkylamines
Substituentsamino sugar; beta-hydroxy acid; hydroxy acid; saccharide; dicarboxylic acid derivative; monosaccharide; oxane; polyol; carboxylic acid ester; secondary alcohol; hemiacetal; 1,2-aminoalcohol; acetal; ether; oxirane; polyamine; carboxylic acid; enolate; carboxylic acid derivative; amine; alcohol; organonitrogen compound; primary amine; primary aliphatic amine
Classification descriptionThis compound belongs to the macrolides and analogues. These are organic compounds containing a lactone ring of at least twelve members.
Pharmacology
IndicationFor the treatment of fungal blepharitis, conjunctivitis, and keratitis caused by susceptible organisms including Fusarium solani keratitis.
PharmacodynamicsNatamycin is an antifungal drug for topical ophthalmic administration. It is a tetraene polyene antibiotic derived from Streptomyces natalensis. It possesses in vitro activity against a variety of yeast and filamentous fungi, including Candida, Aspergillus, Cephalosporium, Fusarium and Penicillium. Although the activity against fungi is dose-related, natamycin is predominantly fungicidal. Natamycin is not effective in vitro against gram-positive or gram-negative bacteria. Topical administration appears to produce effective concentrations of natamycin within the corneal stroma but not in intraocular fluid.
Mechanism of actionLIke other polyene antibiotics, Natamycin inhibits fungal growth by binding to sterols. Specifically, Natamycin binds to ergosterol in the plasma membrane, preventing ergosterol-dependent fusion of vacuoles, as well as membrane fusion and fission. This differs from the mechanism of most other polyene antibiotics, which tend to work by altering fungal membrane permeability instead.
AbsorptionSystemic absorption should not be expected following topical administration, and as with other polyene antibiotics, absorption from the gastrointestinal tract is very poor.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Various Fungus Species
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption - 0.8512
Blood Brain Barrier - 0.9789
Caco-2 permeable - 0.6947
P-glycoprotein substrate Substrate 0.5926
P-glycoprotein inhibitor I Non-inhibitor 0.7063
P-glycoprotein inhibitor II Non-inhibitor 0.9224
Renal organic cation transporter Non-inhibitor 0.9629
CYP450 2C9 substrate Non-substrate 0.7748
CYP450 2D6 substrate Non-substrate 0.8576
CYP450 3A4 substrate Non-substrate 0.5291
CYP450 1A2 substrate Non-inhibitor 0.9046
CYP450 2C9 substrate Non-inhibitor 0.9154
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Non-inhibitor 0.9025
CYP450 3A4 substrate Non-inhibitor 0.8632
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9632
Ames test Non AMES toxic 0.6606
Carcinogenicity Non-carcinogens 0.9448
Biodegradation Not ready biodegradable 0.9718
Rat acute toxicity 2.4181 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.994
hERG inhibition (predictor II) Non-inhibitor 0.9406
Pharmacoeconomics
Manufacturers
  • Alcon laboratories inc
Packagers
Dosage forms
FormRouteStrength
Suspension / dropsOphthalmic
Prices
Unit descriptionCostUnit
Natacyn eye drops14.16USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point290 dec °CPhysProp
water solubility4100 mg/L (at 21 °C)TOMLIN,C (1994)
logP1.1Not Available
logS-3.21ADME Research, USCD
Predicted Properties
PropertyValueSource
water solubility2.78e-01 g/lALOGPS
logP-3.5ALOGPS
logP-1.7ChemAxon
logS-3.4ALOGPS
pKa (strongest acidic)3.58ChemAxon
pKa (strongest basic)9.11ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count13ChemAxon
hydrogen donor count7ChemAxon
polar surface area230.99ChemAxon
rotatable bond count3ChemAxon
refractivity169.88ChemAxon
polarizability68.19ChemAxon
number of rings4ChemAxon
bioavailability0ChemAxon
rule of fiveNoChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Michael A. Eisenschink, Phillip T. Olson, “Fermentation process for producing natamycin.” U.S. Patent US5231014, issued July, 1982.

US5231014
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD00884
KEGG CompoundC08073
PubChem Compound5281099
PubChem Substance46509171
Therapeutic Targets DatabaseDAP001331
PharmGKBPA164744325
RxListhttp://www.rxlist.com/cgi/generic2/natamycin.htm
Drugs.comhttp://www.drugs.com/cdi/natamycin.html
WikipediaNatamycin
ATC CodesA01AB10A07AA03D01AA02G01AA02S01AA10
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsSearched, but no interactions found.
Food InteractionsNot Available

Targets

1. Ergosterol

Kind: small molecule

Organism: Candida albicans

Pharmacological action: yes

Actions: binder

Components

Name UniProt ID Details

References:

  1. te Welscher YM, Jones L, van Leeuwen MR, Dijksterhuis J, de Kruijff B, Eitzen G, Breukink E: Natamycin inhibits vacuole fusion at the priming phase via a specific interaction with ergosterol. Antimicrob Agents Chemother. 2010 Jun;54(6):2618-25. Epub 2010 Apr 12. Pubmed
  2. te Welscher YM, ten Napel HH, Balague MM, Souza CM, Riezman H, de Kruijff B, Breukink E: Natamycin blocks fungal growth by binding specifically to ergosterol without permeabilizing the membrane. J Biol Chem. 2008 Mar 7;283(10):6393-401. Epub 2007 Dec 29. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:12