Identification

Name
Sulfamethizole
Accession Number
DB00576  (APRD00684)
Type
Small Molecule
Groups
Approved, Investigational, Vet Approved
Description

A sulfathiazole antibacterial agent. [PubChem]

Structure
Thumb
Synonyms
  • Rufol
  • Sulfamethizol
  • Sulfaméthizol
  • Sulfamethizole
  • Sulfamethizolum
  • Sulfamethylthiadiazole
  • Sulfametizol
International/Other Brands
Lucosil (Recip) / Rufol (Urgo) / Thiosulfil / Thiosulfil Forte
Categories
UNII
25W8454H16
CAS number
144-82-1
Weight
Average: 270.331
Monoisotopic: 270.024516964
Chemical Formula
C9H10N4O2S2
InChI Key
VACCAVUAMIDAGB-UHFFFAOYSA-N
InChI
InChI=1S/C9H10N4O2S2/c1-6-11-12-9(16-6)13-17(14,15)8-4-2-7(10)3-5-8/h2-5H,10H2,1H3,(H,12,13)
IUPAC Name
4-amino-N-(5-methyl-1,3,4-thiadiazol-2-yl)benzene-1-sulfonamide
SMILES
CC1=NN=C(NS(=O)(=O)C2=CC=C(N)C=C2)S1

Pharmacology

Indication

For the treatment of urinary tract infection

Structured Indications
Not Available
Pharmacodynamics

Sulfamethizole is a sulfonamide antibiotic. 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

Sulfamethizole is a competitive inhibitor of bacterial enzyme dihydropteroate synthetase. The normal para-aminobenzoic acid (PABA) substrate is prevented from binding. The inhibited reaction is necessary in these organisms for the synthesis of folic acid.

TargetActionsOrganism
ADihydropteroate synthase
inhibitor
Escherichia coli (strain K12)
Absorption

Rapidly absorbed.

Volume of distribution
Not Available
Protein binding

98-99%

Metabolism

Hepatic.

Route of elimination
Not Available
Half life

3-8 hours

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Enteric bacteria and other eubacteria
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 Sulfamethizole.Approved, Investigational
MecamylamineThe risk or severity of adverse effects can be increased when Sulfamethizole is combined with Mecamylamine.Approved
Food Interactions
Not Available

References

General References
  1. Ratanajamit C, Skriver MV, Norgaard M, Jepsen P, Schonheyder HC, Sorensen HT: Adverse pregnancy outcome in users of sulfamethizole during pregnancy: a population-based observational study. J Antimicrob Chemother. 2003 Nov;52(5):837-41. Epub 2003 Sep 30. [PubMed:14519675]
  2. Kerrn MB, Frimodt-Moller N, Espersen F: Effects of sulfamethizole and amdinocillin against Escherichia coli strains (with various susceptibilities) in an ascending urinary tract infection mouse model. Antimicrob Agents Chemother. 2003 Mar;47(3):1002-9. [PubMed:12604534]
  3. Watanabe H, Hastings JW: Inhibition of bioluminescence in Photobacterium phosphoreum by sulfamethizole and its stimulation by thymine. Biochim Biophys Acta. 1990 Jun 26;1017(3):229-34. [PubMed:2372557]
External Links
Human Metabolome Database
HMDB14715
KEGG Drug
D00870
KEGG Compound
C08050
PubChem Compound
5328
PubChem Substance
46508656
ChemSpider
5137
BindingDB
50295558
ChEBI
9331
ChEMBL
CHEMBL1191
Therapeutic Targets Database
DAP001202
PharmGKB
PA164781307
Wikipedia
Sulfamethizole
ATC Codes
B05CA04 — SulfamethizoleJ01EB02 — SulfamethizoleD06BA04 — SulfamethizoleG01AE10 — Combinations of sulfonamidesS01AB01 — Sulfamethizole
MSDS
Download (73.1 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentOsteomyelitis1

Pharmacoeconomics

Manufacturers
  • Forest pharmaceuticals inc
  • Wyeth ayerst laboratories
Packagers
Dosage forms
Not Available
Prices
Unit descriptionCostUnit
Methazolamide powder27.0USD g
Methazolamide 50 mg tablet0.72USD tablet
Neptazane 25 mg tablet0.6USD tablet
Methazolamide 25 mg tablet0.48USD tablet
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)208 °CPhysProp
water solubility1050 mg/L (at 37 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP0.54HANSCH,C ET AL. (1995)
logS-2.41ADME Research, USCD
Predicted Properties
PropertyValueSource
Water Solubility0.611 mg/mLALOGPS
logP0.53ALOGPS
logP0.21ChemAxon
logS-2.6ALOGPS
pKa (Strongest Acidic)6.71ChemAxon
pKa (Strongest Basic)1.95ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area97.97 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity66.84 m3·mol-1ChemAxon
Polarizability26.26 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9604
Blood Brain Barrier+0.9388
Caco-2 permeable-0.8956
P-glycoprotein substrateNon-substrate0.8662
P-glycoprotein inhibitor INon-inhibitor0.9232
P-glycoprotein inhibitor IINon-inhibitor0.9308
Renal organic cation transporterNon-inhibitor0.8833
CYP450 2C9 substrateNon-substrate0.7992
CYP450 2D6 substrateNon-substrate0.9115
CYP450 3A4 substrateNon-substrate0.7778
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorNon-inhibitor0.9536
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8658
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8607
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.8636
BiodegradationNot ready biodegradable0.9897
Rat acute toxicity1.8564 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9357
hERG inhibition (predictor II)Non-inhibitor0.9206
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
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a4i-1900000000-d28aaee868ff14cf276c
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0a4i-2930000000-baa3fcc8543e75aae150
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0a4i-6921000000-126773aad654d2eed32d

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 / Organosulfonamides / Thiadiazoles / Heteroaromatic compounds / Aminosulfonyl compounds / Azacyclic compounds / Primary amines / Organopnictogen compounds / Organic oxides
show 1 more
Substituents
Aminobenzenesulfonamide / Benzenesulfonyl group / Aniline or substituted anilines / Organosulfonic acid amide / Azole / Organic sulfonic acid or derivatives / Organosulfonic acid or derivatives / Sulfonyl / Thiadiazole / Aminosulfonyl compound
show 13 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
sulfonamide, thiadiazoles, sulfonamide antibiotic (CHEBI:9331)

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. Watanabe H, Hastings JW: Inhibition of bioluminescence in Photobacterium phosphoreum by sulfamethizole and its stimulation by thymine. Biochim Biophys Acta. 1990 Jun 26;1017(3):229-34. [PubMed:2372557]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid 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 oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Brodersen R, Honore B: Drug binding properties of neonatal albumin. Acta Paediatr Scand. 1989 May;78(3):342-6. [PubMed:2545072]
  2. Agren A, Elofsson R, Meresaar U, Nilsson SO: Complex formation between macromolecules and drugs. 3. A study of the influence of ionic strength and pH. Binding between Aptin, nortriptyline, sulfamethizole or tripelenamine and serum albumin, poly-arginine, poly-lysine, poly-ornithine, protamine or dextran sulfate. Acta Pharm Suec. 1970 Apr;7(2):105-12. [PubMed:5421619]
  3. Nakano NI, Shimamori Y, Yamaguchi S: Mutual displacement interactions in the binding of two drugs to human serum albumin by frontal affinity chromatography. J Chromatogr. 1980 Feb 1;188(2):347-56. [PubMed:7380930]
  4. Angelakou A, Valsami G, Koupparis M, Macheras P: Use of 1-anilino-8-napthalenesulphonate as an ion probe for the potentiometric study of the binding of sulphonamides to bovine serum albumin and plasma. J Pharm Pharmacol. 1993 May;45(5):434-8. [PubMed:8099962]

Drug created on June 13, 2005 07:24 / Updated on November 07, 2017 01:40