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

Structure

Similar Structures

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

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Natacyn	Suspension / drops	50 mg/1mL	Ophthalmic	ALCON LABORATORIES, INC.	1980-12-31	Not applicable

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.

Target	Actions	Organism
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: No interactions found.
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

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
1, 2	Completed	Treatment	Fungal Keratitis	1
3	Completed	Treatment	Eye Infections, Fungal / Ulcerative keratitis	1
3	Enrolling by Invitation	Treatment	Fungal Keratitis / Ulcerative keratitis	1
3	Terminated	Treatment	Fungal Keratitis	1
Not Available	Unknown Status	Treatment	Mycotic Corneal Ulcer	1

Pharmacoeconomics

Manufacturers

Alcon laboratories inc

Packagers

Alcon Laboratories

Dosage forms

Form	Route	Strength
Suspension / drops	Ophthalmic	50 mg/1mL

Prices

Unit description	Cost	Unit
Natacyn eye drops	14.16USD	ml

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Not Available

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	290 dec °C	PhysProp
water solubility	4100 mg/L (at 21 °C)	TOMLIN,C (1994)
logP	1.1	Not Available
logS	-3.21	ADME Research, USCD

Predicted Properties

Property	Value	Source
Water Solubility	0.278 mg/mL	ALOGPS
logP	-3.5	ALOGPS
logP	-1.7	ChemAxon
logS	-3.4	ALOGPS
pKa (Strongest Acidic)	3.58	ChemAxon
pKa (Strongest Basic)	9.11	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	13	ChemAxon
Hydrogen Donor Count	7	ChemAxon
Polar Surface Area	230.99 Å²	ChemAxon
Rotatable Bond Count	3	ChemAxon
Refractivity	169.88 m³·mol^-1	ChemAxon
Polarizability	68.58 Å³	ChemAxon
Number of Rings	4	ChemAxon
Bioavailability	0	ChemAxon
Rule of Five	No	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

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 inhibitor	Non-inhibitor	0.9154
CYP450 2D6 inhibitor	Non-inhibitor	0.9231
CYP450 2C19 inhibitor	Non-inhibitor	0.9025
CYP450 3A4 inhibitor	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

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not 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

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]
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

Details1. Cytochrome P450 3A4

Kind: Protein
Organism: Humans
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

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 December 16, 2018 06:43

Natamycin

Identification

Structure for Natamycin (DB00826)

Pharmacology

Interactions

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Taxonomy

Targets

References

Enzymes

References