DrugBank: Sulfamethazine (DB01582)

targets (1) carriers (1)

Identification

Name

Sulfamethazine

Accession Number

DB01582

Type

small molecule

Groups

approved

Description

A sulfanilamide anti-infective agent. It has a spectrum of antimicrobial action similar to other sulfonamides. [PubChem]

Structure

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

Not Available

Brand names

Not Available

Brand name mixtures

Not Available

Categories

Anti-Infective Agents
Sulfonamides

CAS number

57-68-1

Weight

Average: 278.33
Monoisotopic: 278.083746402

Chemical Formula

C₁₂H₁₄N₄O₂S

InChI Key

InChIKey=ASWVTGNCAZCNNR-UHFFFAOYSA-N

InChI

InChI=1S/C12H14N4O2S/c1-8-7-9(2)15-12(14-8)16-19(17,18)11-5-3-10(13)4-6-11/h3-7H,13H2,1-2H3,(H,14,15,16)

Plain Text

IUPAC Name

4-amino-N-(4,6-dimethylpyrimidin-2-yl)benzene-1-sulfonamide

SMILES

CC1=CC(C)=NC(NS(=O)(=O)C2=CC=C(N)C=C2)=N1

Plain Text

Mass Spec

show (8.1 KB)

Taxonomy

Kingdom

Organic

Classes

Benzenesulfonamides
Sulfanilamides

Substructures

Sulfonyls
Aliphatic and Aryl Amines
Benzene and Derivatives
Benzenesulfonamides
Pyrimidines and Derivatives
Heterocyclic compounds
Aromatic compounds
Sulfanilamides
Sulfonamides
Imines
Cyanamides
Anilines

Pharmacology

Indication

For the treatment bacterial infections causing bronchitis, prostatitis and urinary tract infections.

Pharmacodynamics

Sulfamethazine is a sulfonamide drug that inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid (PABA) for binding to dihydropteroate synthetase (dihydrofolate synthetase). Sulfamethazine is bacteriostatic in nature. Inhibition of dihydrofolic acid synthesis decreases the synthesis of bacterial nucleotides and DNA.

Mechanism of action

Sulfonamides inhibit the enzymatic conversion of pteridine and p-aminobenzoic acid (PABA) to dihydropteroic acid by competing with PABA for binding to dihydrofolate synthetase, an intermediate of tetrahydrofolic acid (THF) synthesis. THF is required for the synthesis of purines and dTMP and inhibition of its synthesis inhibits bacterial growth. Pyrimethamine and trimethoprim inhibit dihydrofolate reductase, another step in THF synthesis, and therefore act synergistically with the sulfonamides.

Absorption

Rapidly absorbed following oral administration.

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Route of elimination

Not Available

Half life

Not Available

Clearance

Not Available

Toxicity

Sulfamethazine may cause nausea, vomiting, diarrhea and hypersensitivity reactions. Hematologic effects such as anemia, agranulocytosis, thrombocytopenia and hemolytic anemia in patients with glucose-6-phosphate dehydrogenase deficiency may also occur. Sulfamethoxazole may displace bilirubin from albumin binding sites causing jaundice or kernicterus in newborns.

Affected organisms

Not Available

Pathways

Not Available

Pharmacoeconomics

Manufacturers

Not Available

Packagers

C.O. Truxton Inc.
Spectrum Pharmaceuticals

Dosage forms

Not Available

Prices

Unit description	Cost	Unit
Sulfamethazine powder	1.74 USD	g

Patents

Not Available

Properties

State

solid

Melting point

198.5 oC

Experimental Properties

Property	Value	Source
water solubility	1.5 mg/mL at 29 oC [MERCK INDEX (1983); at pH 7]	PhysProp
logP	0.89 [BIOBYTE (1995)]	PhysProp

Predicted Properties

Property	Value	Source
water solubility	2.30e-01 g/l	ALOGPS
logP	0.43	ALOGPS
logP	0.65	ChemAxon Molconvert
logS	-3.08	ALOGPS
pKa		ChemAxon Molconvert
hydrogen acceptor count	5	ChemAxon Molconvert
hydrogen donor count	2	ChemAxon Molconvert
polar surface area	97.97	ChemAxon Molconvert
rotatable bond count	2	ChemAxon Molconvert
refractivity	73.38	ChemAxon Molconvert
polarizability	28.80	ChemAxon Molconvert

References

Synthesis Reference

Not Available

General Reference

Not Available

External Links

Resource	Link
PubChem Compound	5327
PubChem Substance	46507146
ChemSpider	5136
ChEBI	102265
ChEMBL	102265
Therapeutic Targets Database	DAP001241
PharmGKB	PA451542
Drug Product Database	0

ATC Codes

J01EB03

AHFS Codes

Not Available

PDB Entries

Not Available

FDA label

Not Available

MSDS

show (73 KB)

Interactions

Drug Interactions

Not Available

Food Interactions

Do not take calcium, aluminium, magnesium or iron supplements within 2 hours of taking this medication.

Targets
1. Dihydropteroate synthase Pharmacological action: yes Actions: inhibitor DHPS catalyzes the formation of the immediate precursor of folic acid. It is implicated in resistance to sulfonamide Organism class: bacterial UniProt ID: P0AC13 Gene: folP Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Hong YL, Hossler PA, Calhoun DH, Meshnick SR: Inhibition of recombinant Pneumocystis carinii dihydropteroate synthetase by sulfa drugs. Antimicrob Agents Chemother. 1995 Aug;39(8):1756-63. Pubmed Friaza V, Morilla R, Respaldiza N, de la Horra C, Calderon EJ: Pneumocystis jiroveci dihydropteroate synthase gene mutations among colonized individuals and Pneumocystis pneumonia patients from Spain. Postgrad Med. 2010 Nov;122(6):24-8. Pubmed Thijssen HH: A simplified radioassay method of dihydropteroate synthetase activity in Escherichia coli and its application for an inhibition study of p-aminobenzoi acid derivatives. Anal Biochem. 1973 Jun;53(2):579-85. Pubmed

Targets

1. Dihydropteroate synthase

Pharmacological action: yes
Actions: inhibitor

DHPS catalyzes the formation of the immediate precursor of folic acid. It is implicated in resistance to sulfonamide

Organism class: bacterial
UniProt ID: P0AC13 Link_out

Gene: folP
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Hong YL, Hossler PA, Calhoun DH, Meshnick SR: Inhibition of recombinant Pneumocystis carinii dihydropteroate synthetase by sulfa drugs. Antimicrob Agents Chemother. 1995 Aug;39(8):1756-63. Pubmed
Friaza V, Morilla R, Respaldiza N, de la Horra C, Calderon EJ: Pneumocystis jiroveci dihydropteroate synthase gene mutations among colonized individuals and Pneumocystis pneumonia patients from Spain. Postgrad Med. 2010 Nov;122(6):24-8. Pubmed
Thijssen HH: A simplified radioassay method of dihydropteroate synthetase activity in Escherichia coli and its application for an inhibition study of p-aminobenzoi acid derivatives. Anal Biochem. 1973 Jun;53(2):579-85. Pubmed

Carriers
1. Serum albumin 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 colloidal osmotic pressure of blood UniProt ID: P02768 Gene: ALB Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Bratlid D, Bergan T: Displacement of albumin-bound antimicrobial agents by bilirubin. Pharmacology. 1976;14(5):464-72. Pubmed 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

Carriers

1. Serum albumin

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 colloidal osmotic pressure of blood

UniProt ID: P02768 Link_out

Gene: ALB

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Bratlid D, Bergan T: Displacement of albumin-bound antimicrobial agents by bilirubin. Pharmacology. 1976;14(5):464-72. Pubmed
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

Comments

Drug created on August 29, 2007 08:54 / Updated on April 19, 2011 15:10

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.