Identification

Name
Ribostamycin
Accession Number
DB03615  (EXPT02786)
Type
Small Molecule
Groups
Approved, Investigational
Description

A broad-spectrum antimicrobial isolated from Streptomyces ribosifidicus. Ribostamycin, along with other aminoglycosides with the DOS (2-deoxystreptamine) subunit, is an important broad-spectrum antibiotic with important use against human immunodeficiency virus and is considered a critically important antimicrobial by the World Health Organization.

Structure
Thumb
Synonyms
  • 5-Amino-2-Aminomethyl-6-[4,6-Diamino-2-(3,4-Dihydroxy-5-Hydroxymethyl-Tetrahydro-Furan-2-Yloxy)-3-Hydroxy-Cyclohexyloxy]-Tetrahydro-Pyran-3,4-Diol
  • Ribastamin
  • RIO
  • Vistamycin
  • Xylostacin
  • Xylostasin
External IDs
Antibiotic SF 733 / SF-733
Product Ingredients
IngredientUNIICASInChI Key
Ribostamycin sulfateQFN1QU7PEN53797-35-6Not applicable
Categories
UNII
2Q5JOU7T53
CAS number
25546-65-0
Weight
Average: 454.4727
Monoisotopic: 454.227493328
Chemical Formula
C17H34N4O10
InChI Key
NSKGQURZWSPSBC-VVPCINPTSA-N
InChI
InChI=1S/C17H34N4O10/c18-2-6-10(24)12(26)8(21)16(28-6)30-14-5(20)1-4(19)9(23)15(14)31-17-13(27)11(25)7(3-22)29-17/h4-17,22-27H,1-3,18-21H2/t4-,5+,6-,7-,8-,9+,10-,11-,12-,13-,14-,15-,16-,17+/m1/s1
IUPAC Name
(2R,3S,4R,5R,6R)-5-amino-2-(aminomethyl)-6-{[(1R,2R,3S,4R,6S)-4,6-diamino-2-{[(2S,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy}-3-hydroxycyclohexyl]oxy}oxane-3,4-diol
SMILES
[H][C@]1(CO)O[C@@]([H])(O[C@]2([H])[C@@]([H])(O)[C@]([H])(N)C[C@]([H])(N)[C@@]2([H])O[C@@]2([H])O[C@]([H])(CN)[C@@]([H])(O)[C@]([H])(O)[C@@]2([H])N)[C@]([H])(O)[C@]1([H])O

Pharmacology

Indication
Not Available
Pharmacodynamics
Not Available
Mechanism of action

Aminoglycosides work by binding to the bacterial 30S ribosomal subunit (some work by binding to the 50S subunit), inhibiting the translocation of the peptidyl-tRNA from the A-site to the P-site and also causing misreading of mRNA, leaving the bacterium unable to synthesize proteins vital to its growth. However, their exact mechanism of action is not fully known.

TargetActionsOrganism
UAminoglycoside N(6')-acetyltransferase type 1Not AvailableSalmonella enteritidis
UAminoglycoside 2'-N-acetyltransferaseNot AvailableMycobacterium tuberculosis
UProtein disulfide-isomeraseNot AvailableHuman
U30S ribosomal protein S12Not AvailableEscherichia coli (strain K12)
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
  • Humans and other mammals
  • Enteric bacteria and other eubacteria
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(4R)-limonene(4R)-limonene may decrease the excretion rate of Ribostamycin which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Ribostamycin which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Ribostamycin which could result in a higher serum level.
AcetaminophenRibostamycin may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
AcetyldigitoxinThe serum concentration of Acetyldigitoxin can be decreased when it is combined with Ribostamycin.
AcetyldigoxinThe serum concentration of Acetyldigoxin can be decreased when it is combined with Ribostamycin.
Acetylsalicylic acidThe risk or severity of nephrotoxicity can be increased when Acetylsalicylic acid is combined with Ribostamycin.
AlclofenacAlclofenac may decrease the excretion rate of Ribostamycin which could result in a higher serum level.
AlcuroniumRibostamycin may increase the respiratory depressant activities of Alcuronium.
Alendronic acidRibostamycin may increase the hypocalcemic activities of Alendronic acid.
Food Interactions
Not Available

References

Synthesis Reference

Eiichi Akita, Tsutomu Tsuchiya, Shinichi Kondo, Shuntaro Yasuda, Sumio Umezawa, Hamao Umezawa, "1-N-((S)-.alpha.-substituted-.omega.-aminoacyl)-neamine or -ribostamycin and the production thereof." U.S. Patent US4008218, issued February, 1974.

US4008218
General References
Not Available
External Links
KEGG Compound
C01759
PubChem Compound
33042
PubChem Substance
46505351
ChemSpider
30581
ChEBI
45257
ChEMBL
CHEMBL221572
Therapeutic Targets Database
DNC001211
HET
RIO
Wikipedia
Ribostamycin
ATC Codes
J01GB10 — Ribostamycin
PDB Entries
1m4g / 1s3z / 2bue / 2et5 / 2fcz / 2kxm / 2n0j / 3c3z / 3dvv / 5iqd
show 1 more

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4RecruitingTreatmentSarcoidosis1

Pharmacoeconomics

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

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)193.5 °CPhysProp
pKa7.7MERCK INDEX (1996)
Predicted Properties
PropertyValueSource
Water Solubility88.7 mg/mLALOGPS
logP-2.9ALOGPS
logP-6.4ChemAxon
logS-0.71ALOGPS
pKa (Strongest Acidic)12.19ChemAxon
pKa (Strongest Basic)9.93ChemAxon
Physiological Charge4ChemAxon
Hydrogen Acceptor Count14ChemAxon
Hydrogen Donor Count10ChemAxon
Polar Surface Area262.38 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity100.17 m3·mol-1ChemAxon
Polarizability44.29 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.8617
Blood Brain Barrier-0.9659
Caco-2 permeable-0.7502
P-glycoprotein substrateNon-substrate0.5164
P-glycoprotein inhibitor INon-inhibitor0.8023
P-glycoprotein inhibitor IINon-inhibitor0.8764
Renal organic cation transporterNon-inhibitor0.7886
CYP450 2C9 substrateNon-substrate0.8231
CYP450 2D6 substrateNon-substrate0.8041
CYP450 3A4 substrateNon-substrate0.6473
CYP450 1A2 substrateNon-inhibitor0.9157
CYP450 2C9 inhibitorNon-inhibitor0.9147
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9034
CYP450 3A4 inhibitorNon-inhibitor0.9471
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8446
Ames testNon AMES toxic0.6934
CarcinogenicityNon-carcinogens0.9505
BiodegradationNot ready biodegradable0.8587
Rat acute toxicity1.4850 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9728
hERG inhibition (predictor II)Non-inhibitor0.81
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 4,5-disubstituted 2-deoxystreptamines. These are 2-deoxystreptamine aminoglycosides that a glycosidically linked to a pyranose of furanose unit at the C4- and C5-positions.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbohydrates and carbohydrate conjugates
Direct Parent
4,5-disubstituted 2-deoxystreptamines
Alternative Parents
O-glycosyl compounds / Aminocyclitols and derivatives / Cyclohexylamines / Cyclohexanols / Oxanes / Monosaccharides / Tetrahydrofurans / 1,2-aminoalcohols / Oxacyclic compounds / Acetals
show 4 more
Substituents
4,5-disubstituted 2-deoxystreptamine / Glycosyl compound / O-glycosyl compound / Aminocyclitol or derivatives / Cyclohexanol / Cyclohexylamine / Cyclitol or derivatives / Monosaccharide / Oxane / Tetrahydrofuran
show 16 more
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
aminoglycoside antibiotic, amino cyclitol glycoside (CHEBI:45257)

Targets

Kind
Protein
Organism
Salmonella enteritidis
Pharmacological action
Unknown
General Function
Protein homodimerization activity
Specific Function
Catalyzes the transfer of an acetyl group from acetyl-CoA to the 6'-amino group of aminoglycoside molecules conferring resistance to antibiotics containing the purpurosamine ring including amikacin...
Gene Name
Not Available
Uniprot ID
Q9R381
Uniprot Name
Aminoglycoside N(6')-acetyltransferase type 1
Molecular Weight
16361.42 Da
Kind
Protein
Organism
Mycobacterium tuberculosis
Pharmacological action
Unknown
General Function
May catalyze the coenzyme A-dependent acetylation of the 2' hydroxyl or amino group of a broad spectrum of aminoglycosides and confer resistance to aminoglycosides (By similarity). In vitro assays show no significant increase of resistance to aminoglycosides, possibly due to low expression in a heterologous system (PubMed:9159528).
Specific Function
Aminoglycoside 2'-n-acetyltransferase activity
Gene Name
aac
Uniprot ID
P9WQG9
Uniprot Name
Aminoglycoside 2'-N-acetyltransferase
Molecular Weight
20037.53 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Protein heterodimerization activity
Specific Function
This multifunctional protein catalyzes the formation, breakage and rearrangement of disulfide bonds. At the cell surface, seems to act as a reductase that cleaves disulfide bonds of proteins attach...
Gene Name
P4HB
Uniprot ID
P07237
Uniprot Name
Protein disulfide-isomerase
Molecular Weight
57115.795 Da
References
  1. Horibe T, Nagai H, Sakakibara K, Hagiwara Y, Kikuchi M: Ribostamycin inhibits the chaperone activity of protein disulfide isomerase. Biochem Biophys Res Commun. 2001 Dec 21;289(5):967-72. [PubMed:11741285]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Unknown
General Function
Trna binding
Specific Function
With S4 and S5 plays an important role in translational accuracy.Interacts with and stabilizes bases of the 16S rRNA that are involved in tRNA selection in the A site and with the mRNA backbone. Lo...
Gene Name
rpsL
Uniprot ID
P0A7S3
Uniprot Name
30S ribosomal protein S12
Molecular Weight
13736.995 Da

Enzymes

Kind
Protein
Organism
Mycobacterium tuberculosis
Pharmacological action
Unknown
General Function
May catalyze the coenzyme A-dependent acetylation of the 2' hydroxyl or amino group of a broad spectrum of aminoglycosides and confer resistance to aminoglycosides (By similarity). In vitro assays show no significant increase of resistance to aminoglycosides, possibly due to low expression in a heterologous system (PubMed:9159528).
Specific Function
Aminoglycoside 2'-n-acetyltransferase activity
Gene Name
aac
Uniprot ID
P9WQG9
Uniprot Name
Aminoglycoside 2'-N-acetyltransferase
Molecular Weight
20037.53 Da

Drug created on June 13, 2005 07:24 / Updated on August 02, 2018 05:09