Identification

Name
Natamycin
Accession Number
DB00826  (APRD01136)
Type
Small Molecule
Groups
Approved
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
  • 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
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
NatacynSuspension / drops50 mg/1mLOphthalmicAlcon, Inc.1980-12-31Not applicableUs
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)
Categories
UNII
8O0C852CPO
CAS number
7681-93-8
Weight
Average: 665.733
Monoisotopic: 665.304740577
Chemical Formula
C33H47NO13
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

Pharmacology

Indication

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

Associated Conditions
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
Toxicity
Not Available
Affected organisms
  • Various Fungus Species
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with Natamycin.Approved, Investigational
AlprazolamThe serum concentration of Alprazolam can be increased when it is combined with Natamycin.Approved, Illicit, Investigational
Amphotericin BThe therapeutic efficacy of Amphotericin B can be decreased when used in combination with Natamycin.Approved, Investigational
AmrinoneThe therapeutic efficacy of Natamycin can be increased when used in combination with Amrinone.Approved
AtorvastatinThe risk or severity of rhabdomyolysis can be increased when Natamycin is combined with Atorvastatin.Approved
AzimilideThe therapeutic efficacy of Natamycin can be increased when used in combination with Azimilide.Investigational
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Natamycin.Investigational
BromocriptineThe serum concentration of Bromocriptine can be increased when it is combined with Natamycin.Approved, Investigational
BuspironeThe metabolism of Buspirone can be decreased when combined with Natamycin.Approved, Investigational
BusulfanThe serum concentration of Busulfan can be increased when it is combined with Natamycin.Approved, Investigational
CaffeineThe metabolism of Caffeine can be decreased when combined with Natamycin.Approved
CarbamazepineThe metabolism of Carbamazepine can be decreased when combined with Natamycin.Approved, Investigational
CerivastatinThe risk or severity of rhabdomyolysis can be increased when Natamycin is combined with Cerivastatin.Approved, Withdrawn
CisaprideThe serum concentration of Cisapride can be increased when it is combined with Natamycin.Approved, Investigational, Withdrawn
CyclosporineThe metabolism of Cyclosporine can be decreased when combined with Natamycin.Approved, Investigational, Vet Approved
DidanosineDidanosine can cause a decrease in the absorption of Natamycin resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
DocetaxelThe metabolism of Docetaxel can be decreased when combined with Natamycin.Approved, Investigational
DofetilideThe serum concentration of Dofetilide can be increased when it is combined with Natamycin.Approved, Investigational
EtravirineThe serum concentration of Etravirine can be increased when it is combined with Natamycin.Approved
FosphenytoinThe serum concentration of Natamycin can be decreased when it is combined with Fosphenytoin.Approved, Investigational
GanciclovirThe metabolism of Ganciclovir can be decreased when combined with Natamycin.Approved, Investigational
HydrocodoneThe metabolism of Hydrocodone can be decreased when combined with Natamycin.Approved, Illicit, Investigational
LovastatinThe risk or severity of rhabdomyolysis can be increased when Natamycin is combined with Lovastatin.Approved, Investigational
MevastatinThe risk or severity of rhabdomyolysis can be increased when Natamycin is combined with Mevastatin.Experimental
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Natamycin.Approved
PitavastatinThe risk or severity of rhabdomyolysis can be increased when Natamycin is combined with Pitavastatin.Approved
ProgesteroneThe absorption of Progesterone can be decreased when combined with Natamycin.Approved, Vet Approved
QuinidineThe serum concentration of Quinidine can be increased when it is combined with Natamycin.Approved, Investigational
RanolazineThe serum concentration of Ranolazine can be increased when it is combined with Natamycin.Approved, Investigational
RifabutinThe serum concentration of Rifabutin can be increased when it is combined with Natamycin.Approved, Investigational
RifapentineThe serum concentration of Rifapentine can be increased when it is combined with Natamycin.Approved, Investigational
RifaximinThe serum concentration of Rifaximin can be increased when it is combined with Natamycin.Approved, Investigational
SolifenacinThe metabolism of Solifenacin can be decreased when combined with Natamycin.Approved
SunitinibThe metabolism of Sunitinib can be decreased when combined with Natamycin.Approved, Investigational
TacrolimusThe metabolism of Tacrolimus can be decreased when combined with Natamycin.Approved, Investigational
ValaciclovirThe metabolism of Valaciclovir can be decreased when combined with Natamycin.Approved, Investigational
WarfarinThe serum concentration of Warfarin can be increased when it is combined with Natamycin.Approved
Food Interactions
Not Available

References

Synthesis Reference

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

US5231014
General References
Not Available
External Links
KEGG Drug
D00884
KEGG Compound
C08073
PubChem Compound
5284447
PubChem Substance
46509171
ChemSpider
10468784
BindingDB
50370755
ChEMBL
CHEMBL1200656
Therapeutic Targets Database
DAP001331
PharmGKB
PA164744325
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Natamycin
ATC Codes
D01AA02 — NatamycinA07AA03 — NatamycinG01AA02 — NatamycinS01AA10 — NatamycinA01AB10 — Natamycin

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1, 2CompletedTreatmentFungal Keratitis1
3CompletedTreatmentEye Infections, Fungal / Ulcerative keratitis1
3Enrolling by InvitationTreatmentFungal Keratitis / Ulcerative keratitis1
3TerminatedTreatmentFungal Keratitis1
Not AvailableUnknown StatusTreatmentMycotic Corneal Ulcer1

Pharmacoeconomics

Manufacturers
  • Alcon laboratories inc
Packagers
  • Alcon Laboratories
Dosage forms
FormRouteStrength
Suspension / dropsOphthalmic50 mg/1mL
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

Taxonomy

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
Aminoglycoside core / Macrolide / Hexose monosaccharide / O-glycosyl compound / Glycosyl compound / Beta-hydroxy acid / Hydroxy acid / Monosaccharide / Dicarboxylic acid or derivatives / Oxane
show 29 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
Not 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]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Kuper JI, D'Aprile M: Drug-Drug interactions of clinical significance in the treatment of patients with Mycobacterium avium complex disease. Clin Pharmacokinet. 2000 Sep;39(3):203-14. [PubMed:11020135]

Drug created on June 13, 2005 07:24 / Updated on September 13, 2018 15:43