Identification

Name
Sulfacytine
Accession Number
DB01298
Type
Small Molecule
Groups
Approved
Description

Sulfacytine is a short-acting sulfonamide. The sulfonamides are synthetic bacteriostatic antibiotics with a wide spectrum against most gram-positive and many gram-negative organisms. However, many strains of an individual species may be resistant. Sulfonamides inhibit multiplication of bacteria by acting as competitive inhibitors of p-aminobenzoic acid in the folic acid metabolism cycle. Bacterial sensitivity is the same for the various sulfonamides, and resistance to one sulfonamide indicates resistance to all. Most sulfonamides are readily absorbed orally. However, parenteral administration is difficult, since the soluble sulfonamide salts are highly alkaline and irritating to the tissues. The sulfonamides are widely distributed throughout all tissues. High levels are achieved in pleural, peritoneal, synovial, and ocular fluids. Although these drugs are no longer used to treat meningitis, CSF levels are high in meningeal infections.

Sulfacytine is a competitive inhibitor of the enzyme dihydropteroate synthetase. It inhibits bacterial synthesis of of dihydrofolic acid by preventing the condensation of the pteridine with para-aminobenzoic acid (PABA), a substrate of the enzyme dihydropteroate synthetase. The inhibited reaction is necessary in these organisms for the synthesis of folic acid.

Structure
Thumb
Synonyms
  • 1-ethyl N4-sulfanilylcytosin
  • 1-ethyl-N-sulfanilylcytosine
  • N-sulfanilyl-l-ethylcytosine
  • Renoquid
  • Sulfacitina
  • Sulfacitine
  • Sulfacitinum
External IDs
CI-636 / NSC-356717
International/Other Brands
Renoquid
Categories
UNII
T795873AJP
CAS number
17784-12-2
Weight
Average: 294.33
Monoisotopic: 294.078661024
Chemical Formula
C12H14N4O3S
InChI Key
SIBQAECNSSQUOD-UHFFFAOYSA-N
InChI
InChI=1S/C12H14N4O3S/c1-2-16-8-7-11(14-12(16)17)15-20(18,19)10-5-3-9(13)4-6-10/h3-8H,2,13H2,1H3,(H,14,15,17)
IUPAC Name
4-amino-N-(1-ethyl-2-oxo-1,2-dihydropyrimidin-4-yl)benzene-1-sulfonamide
SMILES
CCN1C=CC(NS(=O)(=O)C2=CC=C(N)C=C2)=NC1=O

Pharmacology

Indication

Used orally in the treatment of acute urinary tract infections.

Structured Indications
Not Available
Pharmacodynamics

Sulfacytine is a short-acting sulfonamide. The sulfonamides are synthetic bacteriostatic antibiotics with a wide spectrum against most gram-positive and many gram-negative organisms. However, many strains of an individual species may be resistant. Sulfonamides inhibit multiplication of bacteria by acting as competitive inhibitors of p-aminobenzoic acid in the folic acid metabolism cycle. Bacterial sensitivity is the same for the various sulfonamides, and resistance to one sulfonamide indicates resistance to all. Most sulfonamides are readily absorbed orally. However, parenteral administration is difficult, since the soluble sulfonamide salts are highly alkaline and irritating to the tissues. The sulfonamides are widely distributed throughout all tissues. High levels are achieved in pleural, peritoneal, synovial, and ocular fluids. Although these drugs are no longer used to treat meningitis, CSF levels are high in meningeal infections. Their antibacterial action is inhibited by pus.

Mechanism of action

Sulfacytine is a competitive inhibitor of the enzyme dihydropteroate synthetase. It inhibits bacterial synthesis of of dihydrofolic acid by preventing the condensation of the pteridine with para-aminobenzoic acid (PABA), a substrate of the enzyme dihydropteroate synthetase. The inhibited reaction is necessary in these organisms for the synthesis of folic acid.

TargetActionsOrganism
ADihydropteroate synthase
inhibitor
Escherichia coli (strain K12)
Absorption

Well absorbed following oral administration.

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
  • Bacteria
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
DexketoprofenThe risk or severity of adverse effects can be increased when Dexketoprofen is combined with Sulfacytine.Approved, Investigational
MecamylamineThe risk or severity of adverse effects can be increased when Sulfacytine is combined with Mecamylamine.Approved
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB15412
PubChem Compound
5322
PubChem Substance
46505483
ChemSpider
5131
ChEBI
135230
ChEMBL
CHEMBL1201056
Therapeutic Targets Database
DAP001201
PharmGKB
PA164754808
ATC Codes
G01AE10 — Combinations of sulfonamides

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
melting point (°C)166.5 °CPhysProp
water solubility1750 mg/L (at 37 °C)MERCK INDEX (1996); pH 5
Predicted Properties
PropertyValueSource
Water Solubility0.468 mg/mLALOGPS
logP0.51ALOGPS
logP0.055ChemAxon
logS-2.8ALOGPS
pKa (Strongest Acidic)10.55ChemAxon
pKa (Strongest Basic)2.17ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area104.86 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity75.49 m3·mol-1ChemAxon
Polarizability29.43 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9934
Blood Brain Barrier+0.899
Caco-2 permeable-0.6162
P-glycoprotein substrateNon-substrate0.7261
P-glycoprotein inhibitor INon-inhibitor0.8802
P-glycoprotein inhibitor IINon-inhibitor0.8838
Renal organic cation transporterNon-inhibitor0.8709
CYP450 2C9 substrateNon-substrate0.5727
CYP450 2D6 substrateNon-substrate0.8572
CYP450 3A4 substrateNon-substrate0.7104
CYP450 1A2 substrateNon-inhibitor0.8277
CYP450 2C9 inhibitorNon-inhibitor0.6327
CYP450 2D6 inhibitorNon-inhibitor0.8413
CYP450 2C19 inhibitorNon-inhibitor0.7461
CYP450 3A4 inhibitorNon-inhibitor0.6874
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7815
Ames testNon AMES toxic0.7561
CarcinogenicityNon-carcinogens0.7885
BiodegradationNot ready biodegradable0.9959
Rat acute toxicity1.9655 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9493
hERG inhibition (predictor II)Non-inhibitor0.771
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 GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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 aminobenzenesulfonamides. These are organic compounds containing a benzenesulfonamide moiety with an amine group attached to the benzene ring.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzenesulfonamides
Direct Parent
Aminobenzenesulfonamides
Alternative Parents
Benzenesulfonyl compounds / Aniline and substituted anilines / Pyrimidones / Organosulfonamides / Imidolactams / Hydropyrimidines / Heteroaromatic compounds / Aminosulfonyl compounds / Azacyclic compounds / Primary amines
show 4 more
Substituents
Aminobenzenesulfonamide / Benzenesulfonyl group / Aniline or substituted anilines / Pyrimidone / Hydropyrimidine / Pyrimidine / Organosulfonic acid amide / Imidolactam / Organic sulfonic acid or derivatives / Organosulfonic acid or derivatives
show 16 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Metal ion binding
Specific Function
Catalyzes the condensation of para-aminobenzoate (pABA) with 6-hydroxymethyl-7,8-dihydropterin diphosphate (DHPt-PP) to form 7,8-dihydropteroate (H2Pte), the immediate precursor of folate derivatives.
Gene Name
folP
Uniprot ID
P0AC13
Uniprot Name
Dihydropteroate synthase
Molecular Weight
30614.855 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Hughes J, Roberts LC, Coppridge AJ: Sulfacytine: a new sulfonamide. Double-blind comparison with sulfisoxazole in acute uncomplicated urinary tract infections. J Urol. 1975 Dec;114(6):912-4. [PubMed:1195474]

Drug created on June 30, 2007 08:20 / Updated on November 09, 2017 02:58