Natamycin

Identification

Summary

Natamycin is a macrolide antifungal used to treat fungal infections of the eye.

Brand Names
Natacyn
Generic Name
Natamycin
DrugBank Accession Number
DB00826
Background

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

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 665.733
Monoisotopic: 665.304740577
Chemical Formula
C33H47NO13
Synonyms
  • Natamicina
  • Natamycin
  • Natamycine
  • Natamycinum
  • Pimaracin
  • Pimaricin
External IDs
  • A-5283
  • Antibiotic A-5283
  • CL 12,625
  • CL 12625
  • E 235
  • E-235
  • INS NO.235
  • INS-235

Pharmacology

Indication

For the treatment of fungal blepharitis, conjunctivitis, and keratitis caused by susceptible organisms including Fusarium solani keratitis.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Natamycin 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 action

Like 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.

TargetActionsOrganism
AErgosterol
binder
Candida albicans
Absorption

Systemic absorption should not be expected following topical administration, and as with other polyene antibiotics, absorption from the gastrointestinal tract is very poor.

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
Adverseeffects
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
EstetrolThe therapeutic efficacy of Estetrol can be decreased when used in combination with Natamycin.
Vibrio cholerae CVD 103-HgR strain live antigenThe therapeutic efficacy of Vibrio cholerae CVD 103-HgR strain live antigen can be decreased when used in combination with Natamycin.
Interactions
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Food Interactions
No interactions found.

Products

Products2
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International/Other Brands
Delvocid / Fukricin (Sanbe) / InfectoMyk (Infectopharm) / N-Mycin (Aristopharma) / Natadrops (Cipla) / Natamet (Sun) / Natamycyna (Unia) / Natezhen (Alcon) / Natoph (Ibn Sina) / Natoptic (FDC) / Optinat (Jayson) / Pimafucin (Astellas) / Pimafusin (Elder) / Pimaricin (Senju Seiyaku)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
NatacynSuspension / drops50 mg/1mLOphthalmicEyevance Pharmaceuticals2021-06-12Not applicableUS flag
NatacynSuspension / drops50 mg/1mLOphthalmicALCON LABORATORIES, INC.1980-12-31Not applicableUS flag

Categories

ATC Codes
G01AA02 — NatamycinD01AA02 — NatamycinA01AB10 — NatamycinS01AA10 — NatamycinA07AA03 — Natamycin
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This 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.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbohydrates and carbohydrate conjugates
Direct Parent
Aminoglycosides
Alternative Parents
Macrolides and analogues / Hexoses / O-glycosyl compounds / Beta hydroxy acids and derivatives / Oxanes / Dicarboxylic acids and derivatives / Enoate esters / Amino acids / 1,2-aminoalcohols / Lactones
show 13 more
Substituents
1,2-aminoalcohol / Acetal / Alcohol / Aliphatic heteropolycyclic compound / Alpha,beta-unsaturated carboxylic ester / Amine / Amino acid / Amino acid or derivatives / Aminoglycoside core / Beta-hydroxy acid
show 29 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
Not Available
Affected organisms
  • Various Fungus Species

Chemical Identifiers

UNII
8O0C852CPO
CAS number
7681-93-8
InChI Key
NCXMLFZGDNKEPB-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[C@H](O)C[C@]3(O)C[C@H](O)[C@@H](C(O)=O)[C@]([H])(C[C@@H](O[C@]4([H])O[C@H](C)[C@@H](O)[C@H](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

References

Synthesis Reference

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

US5231014
General References
  1. FDA Approved Drug Products: Natacyn (natamycin) suspension [Link]
KEGG Drug
D00884
KEGG Compound
C08073
PubChem Compound
5284447
PubChem Substance
46509171
ChemSpider
10468784
BindingDB
50370755
RxNav
7268
ChEMBL
CHEMBL1200656
ZINC
ZINC000008220909
Therapeutic Targets Database
DAP001331
PharmGKB
PA164744325
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Natamycin

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentEye Infections, Fungal / Ulcerative keratitis1
3CompletedTreatmentFungal Keratitis / Ulcerative keratitis1
3TerminatedTreatmentFungal Keratitis1
2, 3Unknown StatusTreatmentInfections, Fungal1
1, 2CompletedTreatmentFungal Keratitis1
Not AvailableUnknown StatusTreatmentMycotic Corneal Ulcer1

Pharmacoeconomics

Manufacturers
  • Alcon laboratories inc
Packagers
  • Alcon Laboratories
Dosage Forms
FormRouteStrength
Solution / dropsOphthalmic
Suspension / dropsOphthalmic50 mg/1mL
SuspensionOphthalmic
SuspensionConjunctival; Ophthalmic50 mg
SolutionOphthalmic5 %
CreamTopical
Prices
Unit descriptionCostUnit
Natacyn eye drops14.16USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)290 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 FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Drugtargets2
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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. [Article]
  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. [Article]

Drug created on June 13, 2005 13:24 / Updated on August 09, 2021 16:43