Apramycin

Identification

Name
Apramycin
Accession Number
DB04626
Type
Small Molecule
Groups
Experimental, Vet approved
Description

Apramycin is an aminoglycoside antibiotic and has a bactericidal action against many gram-negative bacteria. Apramycin is a structurally unique antibiotic that contains a bicyclic sugar moiety and a monosubstituted deoxystreptamine. It is not approved for use in humans.

Structure
Thumb
Synonyms
  • apramicina
  • Nebramycin II
External IDs
EL-857
Product Ingredients
IngredientUNIICASInChI Key
Apramycin sulfate8UYL6NAZ3Q65710-07-8Not applicable
Categories
UNII
388K3TR36Z
CAS number
37321-09-8
Weight
Average: 539.5771
Monoisotopic: 539.280257179
Chemical Formula
C21H41N5O11
InChI Key
XZNUGFQTQHRASN-XQENGBIVSA-N
InChI
InChI=1S/C21H41N5O11/c1-26-11-14(30)18-8(33-20(11)37-21-16(32)13(29)10(25)9(4-27)34-21)3-7(24)19(36-18)35-17-6(23)2-5(22)12(28)15(17)31/h5-21,26-32H,2-4,22-25H2,1H3/t5-,6+,7-,8+,9-,10-,11+,12+,13+,14-,15-,16-,17-,18+,19+,20-,21-/m1/s1
IUPAC Name
(2R,3R,4S,5S,6S)-2-{[(2R,3S,4R,4aR,6S,7R,8aS)-7-amino-6-{[(1R,2R,3S,4R,6S)-4,6-diamino-2,3-dihydroxycyclohexyl]oxy}-4-hydroxy-3-(methylamino)-octahydropyrano[3,2-b]pyran-2-yl]oxy}-5-amino-6-(hydroxymethyl)oxane-3,4-diol
SMILES
CN[C@H]1[C@@H](O)[C@H]2O[C@H](O[C@@H]3[C@@H](N)C[C@@H](N)[C@H](O)[C@H]3O)[C@H](N)C[C@@H]2O[C@@H]1O[C@H]1O[C@H](CO)[C@@H](N)[C@H](O)[C@H]1O

Pharmacology

Indication

For the treatment of bacterial infections in animals.

Pharmacodynamics
Not Available
Mechanism of action

Apramycin stands out among aminoglycosides for its mechanism of action which is based on blocking translocation and its ability to bind also to the eukaryotic decoding site despite differences in key residues required for apramycin recognition by the bacterial target. The drug binds in the deep groove of the RNA which forms a continuously stacked helix comprising non-canonical C.A and G.A base pairs and a bulged-out adenine. The binding mode of apramycin at the human decoding-site RNA is distinct from aminoglycoside recognition of the bacterial target, suggesting a molecular basis for the actions of apramycin in eukaryotes and bacteria.

TargetActionsOrganism
U16S rRNANot AvailableEnteric bacteria and other eubacteria
Absorption
Not Available
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
  • Enteric bacteria and other eubacteria
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of bleeding can be increased when Apramycin is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding can be increased when Apramycin is combined with (S)-Warfarin.
1,10-PhenanthrolineThe therapeutic efficacy of 1,10-Phenanthroline can be decreased when used in combination with Apramycin.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when Apramycin is combined with 4-hydroxycoumarin.
AbacavirApramycin may decrease the excretion rate of Abacavir which could result in a higher serum level.
AcarboseApramycin may decrease the excretion rate of Acarbose which could result in a higher serum level.
AceclofenacThe risk or severity of nephrotoxicity can be increased when Aceclofenac is combined with Apramycin.
AcemetacinThe risk or severity of nephrotoxicity can be increased when Acemetacin is combined with Apramycin.
AcenocoumarolThe risk or severity of bleeding can be increased when Apramycin is combined with Acenocoumarol.
AcetaminophenApramycin may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
Food Interactions
Not Available

References

Synthesis Reference

Koji Tomita, Hiroshi Tsukiura, Hiroshi Kawaguchi, "Fermentation process for producing apramycin and nebramycin factor V'." U.S. Patent US4032404, issued December, 1974.

US4032404
General References
  1. Hermann T, Tereshko V, Skripkin E, Patel DJ: Apramycin recognition by the human ribosomal decoding site. Blood Cells Mol Dis. 2007 May-Jun;38(3):193-8. Epub 2007 Jan 29. [PubMed:17258916]
  2. Kondo J, Francois B, Urzhumtsev A, Westhof E: Crystal structure of the Homo sapiens cytoplasmic ribosomal decoding site complexed with apramycin. Angew Chem Int Ed Engl. 2006 May 12;45(20):3310-4. [PubMed:16596680]
  3. Han Q, Zhao Q, Fish S, Simonsen KB, Vourloumis D, Froelich JM, Wall D, Hermann T: Molecular recognition by glycoside pseudo base pairs and triples in an apramycin-RNA complex. Angew Chem Int Ed Engl. 2005 Apr 29;44(18):2694-700. [PubMed:15849690]
External Links
KEGG Drug
D02322
KEGG Compound
C01555
PubChem Compound
3081545
PubChem Substance
46509143
ChemSpider
2339128
ChEBI
2790
ChEMBL
CHEMBL1230961
Therapeutic Targets Database
DNC000243
HET
AM2
Wikipedia
Apramycin
PDB Entries
1yrj / 2g5k / 2m4q / 2oe5 / 2oe8 / 4aqy / 4k31 / 6mn4
MSDS
Download (40.6 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
pKa8.5MERCK INDEX (1996)
Predicted Properties
PropertyValueSource
Water Solubility53.3 mg/mLALOGPS
logP-2.8ALOGPS
logP-6.5ChemAxon
logS-1ALOGPS
pKa (Strongest Acidic)12.29ChemAxon
pKa (Strongest Basic)9.73ChemAxon
Physiological Charge5ChemAxon
Hydrogen Acceptor Count16ChemAxon
Hydrogen Donor Count11ChemAxon
Polar Surface Area283.64 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity120.91 m3·mol-1ChemAxon
Polarizability54.29 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.8007
Blood Brain Barrier-0.9898
Caco-2 permeable-0.7556
P-glycoprotein substrateSubstrate0.568
P-glycoprotein inhibitor INon-inhibitor0.8164
P-glycoprotein inhibitor IINon-inhibitor0.9619
Renal organic cation transporterNon-inhibitor0.885
CYP450 2C9 substrateNon-substrate0.7737
CYP450 2D6 substrateNon-substrate0.8285
CYP450 3A4 substrateNon-substrate0.544
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9196
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.9234
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8708
Ames testAMES toxic0.5193
CarcinogenicityNon-carcinogens0.9671
BiodegradationNot ready biodegradable0.9023
Rat acute toxicity2.2488 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9812
hERG inhibition (predictor II)Non-inhibitor0.8385
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 aminocyclitol glycosides. These are organic compounds containing an amicocyclitol moiety glycosidically linked to a carbohydrate moiety. There are two major classes of aminoglycosides containing a 2-streptamine core. They are called 4,5- and 4,6-disubstituted 2-deoxystreptamines.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbohydrates and carbohydrate conjugates
Direct Parent
Aminocyclitol glycosides
Alternative Parents
Hexoses / Aminocyclitols and derivatives / Cyclohexylamines / Cyclohexanols / Oxanes / 1,3-aminoalcohols / 1,2-aminoalcohols / Oxacyclic compounds / Dialkylamines / Acetals
show 4 more
Substituents
Amino cyclitol glycoside / Hexose monosaccharide / Aminocyclitol or derivatives / Cyclohexylamine / Cyclohexanol / Oxane / Cyclitol or derivatives / Monosaccharide / 1,3-aminoalcohol / Cyclic alcohol
show 17 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
organic heterobicyclic compound, aminoglycoside, 2-deoxystreptamine derivative (CHEBI:2790)

Targets

1. 16S rRNA
Kind
Nucleotide
Organism
Enteric bacteria and other eubacteria
Pharmacological action
Unknown
References
  1. Woodcock J, Moazed D, Cannon M, Davies J, Noller HF: Interaction of antibiotics with A- and P-site-specific bases in 16S ribosomal RNA. EMBO J. 1991 Oct;10(10):3099-103. [PubMed:1915283]
  2. Kondo J, Francois B, Urzhumtsev A, Westhof E: Crystallographic studies of Homo sapiens ribosomal decoding A site complexed with aminoglycosides. Nucleic Acids Symp Ser (Oxf). 2005;(49):253-4. [PubMed:17150729]

Drug created on September 11, 2007 11:49 / Updated on November 02, 2018 08:54