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Identification
NameNatamycin
Accession NumberDB00826  (APRD01136)
TypeSmall Molecule
GroupsApproved
DescriptionAmphoteric macrolide antifungal antibiotic from Streptomyces natalensis or S. chattanoogensis. It is used for a variety of fungal infections, mainly topically. [PubChem]
Structure
Thumb
Synonyms
Natamicina
Natamycin
Natamycine
Natamycinum
Pimaracin
Pimaricin
External Identifiers
  • A-5283
  • Antibiotic A-5283
  • CL 12,625
  • CL 12625
  • E 235
  • E-235
  • INS NO.235
  • INS-235
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Natacynsuspension/ drops50 mg/mLophthalmicAlcon Laboratories, Inc.1980-12-31Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
DelvocidNot Available
FukricinSanbe
InfectoMykInfectopharm
N-MycinAristopharma
NatadropsCipla
NatametSun
NatamycynaUnia
NatezhenAlcon
NatophIbn Sina
NatopticFDC
OptinatJayson
PimafucinAstellas
PimafusinElder
PimaricinSenju Seiyaku
Brand mixturesNot Available
SaltsNot Available
Categories
UNII8O0C852CPO
CAS number7681-93-8
WeightAverage: 665.733
Monoisotopic: 665.304740577
Chemical FormulaC33H47NO13
InChI KeyNCXMLFZGDNKEPB-FFPOYIOWSA-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,8E,12R,14E,16E,18E,20E,22R,24S,25R,26S)-22-{[(2R,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[22.3.1.0⁵,⁷]octacosa-8,14,16,18,20-pentaene-25-carboxylic acid
SMILES
[H][C@@]12C[[email protected]](O)C[C@]3(O)C[[email protected]](O)[C@@H](C(O)=O)[C@]([H])(C[C@@H](O[C@]4([H])O[[email protected]](C)[C@@H](O)[[email protected]](N)[C@@H]4O)\C=C\C=C\C=C\C=C\C[C@@H](C)OC(=O)\C=C\[C@@]1([H])O2)O3
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as aminoglycosides. These are molecules or a portion of a molecule composed of amino-modified sugars.
KingdomOrganic compounds
Super ClassOrganic oxygen compounds
ClassOrganooxygen compounds
Sub ClassCarbohydrates and carbohydrate conjugates
Direct ParentAminoglycosides
Alternative Parents
Substituents
  • Aminoglycoside core
  • Macrolide
  • Hexose monosaccharide
  • O-glycosyl compound
  • Glycosyl compound
  • Beta-hydroxy acid
  • Hydroxy acid
  • Monosaccharide
  • Oxane
  • Dicarboxylic acid or derivatives
  • Enoate ester
  • Alpha,beta-unsaturated carboxylic ester
  • Carboxylic acid ester
  • 1,2-aminoalcohol
  • Hemiacetal
  • Amino acid
  • Lactone
  • Amino acid or derivatives
  • Secondary alcohol
  • Acetal
  • Oxacycle
  • Carboxylic acid derivative
  • Organoheterocyclic compound
  • Carboxylic acid
  • Dialkyl ether
  • Oxirane
  • Ether
  • Polyol
  • Alcohol
  • Amine
  • Organic oxide
  • Primary amine
  • Hydrocarbon derivative
  • Organic nitrogen compound
  • Carbonyl group
  • Organonitrogen compound
  • Primary aliphatic amine
  • Aliphatic heteropolycyclic compound
Molecular FrameworkAliphatic heteropolycyclic compounds
External DescriptorsNot Available
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.
Related Articles
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
MetabolismNot Available
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
PropertyValueProbability
Human Intestinal Absorption-0.8512
Blood Brain Barrier-0.9789
Caco-2 permeable-0.6947
P-glycoprotein substrateSubstrate0.5926
P-glycoprotein inhibitor INon-inhibitor0.7063
P-glycoprotein inhibitor IINon-inhibitor0.9224
Renal organic cation transporterNon-inhibitor0.9629
CYP450 2C9 substrateNon-substrate0.7748
CYP450 2D6 substrateNon-substrate0.8576
CYP450 3A4 substrateNon-substrate0.5291
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.9154
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8632
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9632
Ames testNon AMES toxic0.6606
CarcinogenicityNon-carcinogens0.9448
BiodegradationNot ready biodegradable0.9718
Rat acute toxicity2.4181 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.994
hERG inhibition (predictor II)Non-inhibitor0.9406
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Alcon laboratories inc
Packagers
Dosage forms
FormRouteStrength
Suspension/ dropsophthalmic50 mg/mL
Prices
Unit descriptionCostUnit
Natacyn eye drops14.16USD ml
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 Solubility0.278 mg/mLALOGPS
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 Area230.99 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity169.88 m3·mol-1ChemAxon
Polarizability68.58 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
References
Synthesis Reference

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

US5231014
General ReferencesNot Available
External Links
ATC CodesD01AA02A07AA03S01AA10A01AB10G01AA02
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AmlodipineThe risk or severity of adverse effects can be increased when Natamycin is combined with Amlodipine.
Amphotericin BThe therapeutic efficacy of Amphotericin B can be decreased when used in combination with Natamycin.
AmrinoneThe risk or severity of adverse effects can be increased when Natamycin is combined with Amrinone.
AzelnidipineThe risk or severity of adverse effects can be increased when Natamycin is combined with Azelnidipine.
AzimilideThe risk or severity of adverse effects can be increased when Natamycin is combined with Azimilide.
BarnidipineThe risk or severity of adverse effects can be increased when Natamycin is combined with Barnidipine.
BenidipineThe risk or severity of adverse effects can be increased when Natamycin is combined with Benidipine.
BepridilThe risk or severity of adverse effects can be increased when Natamycin is combined with Bepridil.
BuspironeThe metabolism of Buspirone can be decreased when combined with Natamycin.
BusulfanThe serum concentration of Busulfan can be increased when it is combined with Natamycin.
CilnidipineThe risk or severity of adverse effects can be increased when Natamycin is combined with Cilnidipine.
CinnarizineThe risk or severity of adverse effects can be increased when Natamycin is combined with Cinnarizine.
CisaprideThe serum concentration of Cisapride can be increased when it is combined with Natamycin.
ConivaptanThe metabolism of Conivaptan can be decreased when combined with Natamycin.
CyclosporineThe metabolism of Cyclosporine can be decreased when combined with Natamycin.
DarodipineThe risk or severity of adverse effects can be increased when Natamycin is combined with Darodipine.
DidanosineDidanosine can cause a decrease in the absorption of Natamycin resulting in a reduced serum concentration and potentially a decrease in efficacy.
DiltiazemThe risk or severity of adverse effects can be increased when Natamycin is combined with Diltiazem.
DocetaxelThe metabolism of Docetaxel can be decreased when combined with Natamycin.
DofetilideThe metabolism of Dofetilide can be decreased when combined with Natamycin.
DotarizineThe risk or severity of adverse effects can be increased when Natamycin is combined with Dotarizine.
EfonidipineThe risk or severity of adverse effects can be increased when Natamycin is combined with Efonidipine.
EperisoneThe risk or severity of adverse effects can be increased when Natamycin is combined with Eperisone.
EtravirineThe serum concentration of Etravirine can be increased when it is combined with Natamycin.
FelodipineThe risk or severity of adverse effects can be increased when Natamycin is combined with Felodipine.
FendilineThe risk or severity of adverse effects can be increased when Natamycin is combined with Fendiline.
FlunarizineThe risk or severity of adverse effects can be increased when Natamycin is combined with Flunarizine.
FosphenytoinThe serum concentration of Natamycin can be decreased when it is combined with Fosphenytoin.
GabapentinThe risk or severity of adverse effects can be increased when Natamycin is combined with Gabapentin.
IsradipineThe risk or severity of adverse effects can be increased when Natamycin is combined with Isradipine.
LacidipineThe risk or severity of adverse effects can be increased when Natamycin is combined with Lacidipine.
LamotrigineThe risk or severity of adverse effects can be increased when Natamycin is combined with Lamotrigine.
LercanidipineThe risk or severity of adverse effects can be increased when Natamycin is combined with Lercanidipine.
LosartanThe metabolism of Losartan can be decreased when combined with Natamycin.
Magnesium SulfateThe risk or severity of adverse effects can be increased when Natamycin is combined with Magnesium Sulfate.
ManidipineThe risk or severity of adverse effects can be increased when Natamycin is combined with Manidipine.
MibefradilThe risk or severity of adverse effects can be increased when Natamycin is combined with Mibefradil.
NicardipineThe risk or severity of adverse effects can be increased when Natamycin is combined with Nicardipine.
NifedipineThe risk or severity of adverse effects can be increased when Natamycin is combined with Nifedipine.
NiguldipineThe risk or severity of adverse effects can be increased when Natamycin is combined with Niguldipine.
NiludipineThe risk or severity of adverse effects can be increased when Natamycin is combined with Niludipine.
NilvadipineThe risk or severity of adverse effects can be increased when Natamycin is combined with Nilvadipine.
NimesulideThe risk or severity of adverse effects can be increased when Natamycin is combined with Nimesulide.
NimodipineThe risk or severity of adverse effects can be increased when Natamycin is combined with Nimodipine.
NisoldipineThe risk or severity of adverse effects can be increased when Natamycin is combined with Nisoldipine.
NitrendipineThe risk or severity of adverse effects can be increased when Natamycin is combined with Nitrendipine.
PerhexilineThe risk or severity of adverse effects can be increased when Natamycin is combined with Perhexiline.
PhenytoinThe serum concentration of Phenytoin can be increased when it is combined with Natamycin.
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Natamycin.
PimozideNatamycin may increase the arrhythmogenic activities of Pimozide.
PinaveriumThe risk or severity of adverse effects can be increased when Natamycin is combined with Pinaverium.
PregabalinThe risk or severity of adverse effects can be increased when Natamycin is combined with Pregabalin.
PrenylamineThe risk or severity of adverse effects can be increased when Natamycin is combined with Prenylamine.
ProgesteroneThe therapeutic efficacy of Progesterone can be decreased when used in combination with Natamycin.
QuinidineThe metabolism of Quinidine can be decreased when combined with Natamycin.
RanolazineThe metabolism of Ranolazine can be decreased when combined with Natamycin.
RisedronateThe risk or severity of adverse effects can be increased when Natamycin is combined with Risedronate.
SolifenacinThe metabolism of Solifenacin can be decreased when combined with Natamycin.
SucralfateSucralfate can cause a decrease in the absorption of Natamycin resulting in a reduced serum concentration and potentially a decrease in efficacy.
SunitinibThe metabolism of Sunitinib can be decreased when combined with Natamycin.
TacrolimusThe metabolism of Tacrolimus can be decreased when combined with Natamycin.
Tolfenamic AcidThe risk or severity of adverse effects can be increased when Natamycin is combined with Tolfenamic Acid.
TranilastThe risk or severity of adverse effects can be increased when Natamycin is combined with Tranilast.
VerapamilThe risk or severity of adverse effects can be increased when Natamycin is combined with Verapamil.
XylometazolineThe risk or severity of adverse effects can be increased when Natamycin is combined with Xylometazoline.
ZiconotideThe risk or severity of adverse effects can be increased when Natamycin is combined with Ziconotide.
ZolpidemThe serum concentration of Zolpidem can be increased when it is combined with Natamycin.
Food InteractionsNot Available

Targets

1. Ergosterol
Kind
Small molecule
Organism
Candida albicans
Pharmacological action
yes
Actions
binder
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. doi: 10.1128/AAC.01794-09. Epub 2010 Apr 12. [PubMed:20385867 ]
  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. doi: 10.1074/jbc.M707821200. Epub 2007 Dec 29. [PubMed:18165687 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23