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Identification
NameSulfadoxine
Accession NumberDB01299
TypeSmall Molecule
GroupsApproved
Description

A long acting sulfonamide that is used, usually in combination with other drugs, for respiratory, urinary tract, and malarial infections. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
4-Sulfanilamido-5,6-dimethoxypyrimidineNot AvailableNot Available
SulfadoxinaNot AvailableNot Available
SulfadoxineNot AvailableNot Available
SulfadoxinumNot AvailableNot Available
SulforthomidineNot AvailableNot Available
SulphadoxineNot AvailableNot Available
SulphormethoxineNot AvailableNot Available
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
CategoriesNot Available
CAS number2447-57-6
WeightAverage: 310.329
Monoisotopic: 310.073575646
Chemical FormulaC12H14N4O4S
InChI KeyPJSFRIWCGOHTNF-UHFFFAOYSA-N
InChI
InChI=1S/C12H14N4O4S/c1-19-10-11(14-7-15-12(10)20-2)16-21(17,18)9-5-3-8(13)4-6-9/h3-7H,13H2,1-2H3,(H,14,15,16)
IUPAC Name
4-amino-N-(5,6-dimethoxypyrimidin-4-yl)benzene-1-sulfonamide
SMILES
COC1=NC=NC(NS(=O)(=O)C2=CC=C(N)C=C2)=C1OC
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzenesulfonamides
Direct ParentAminobenzenesulfonamides
Alternative Parents
Substituents
  • Aminobenzenesulfonamide
  • Sulfonylaniline
  • Substituted aniline
  • Aniline
  • Aminopyrimidine
  • Alkyl aryl ether
  • Imidolactam
  • Pyrimidine
  • Primary aromatic amine
  • Heteroaromatic compound
  • Aminosulfonyl compound
  • Sulfonyl
  • Sulfonic acid derivative
  • Sulfonamide
  • Azacycle
  • Organoheterocyclic compound
  • Ether
  • Hydrocarbon derivative
  • Primary amine
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationSulfadoxine is used in combination with pyrimethamine for the treatment or prevention of malaria. It can also be used to treat various infections in livestock as well. Sulfadoxine and pyrimethamine is indicated for the treatment of Plasmodium falciparum malaria in those patients in whom chloroquine resistance is suspected.
PharmacodynamicsSulfadoxine helps inhibit the enzyme dihydropteroate synthetase which is an enzyme necessary in the conversion of PABA to folic acid. As folic acid is vital to the synthesis, repair, and methylation of DNA which is vital to cell growth in Plasmodium falciparum. With this vital nutrient lacking, the parasite has difficulty in reproducing.
Mechanism of actionSulfadoxine is a sulfa drug, often used in combination with pyrimethamine to treat malaria. This medicine may also be used to prevent malaria in people who are living in, or will be traveling to, an area where there is a chance of getting malaria. Sulfadoxine targets Plasmodium dihydropteroate synthase and dihydrofolate reductase. Sulfa drugs or Sulfonamides are antimetabolites. They compete with para-aminobenzoic acid (PABA) for incorporation into folic acid. The action of sulfonamides exploits the difference between mammal cells and other kinds of cells in their folic acid metabolism. All cells require folic acid for growth. Folic acid (as a vitamin) diffuses or is transported into human cells. However, folic acid cannot cross bacterial (and certain protozoan) cell walls by diffusion or active transport. For this reason bacteria must synthesize folic acid from p-aminobenzoic acid.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9602
Blood Brain Barrier-0.5345
Caco-2 permeable-0.59
P-glycoprotein substrateNon-substrate0.8126
P-glycoprotein inhibitor INon-inhibitor0.832
P-glycoprotein inhibitor IINon-inhibitor0.8892
Renal organic cation transporterNon-inhibitor0.9164
CYP450 2C9 substrateNon-substrate0.693
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.6464
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 substrateNon-inhibitor0.9071
CYP450 2D6 substrateNon-inhibitor0.9231
CYP450 2C19 substrateNon-inhibitor0.9026
CYP450 3A4 substrateNon-inhibitor0.8703
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6052
Ames testNon AMES toxic0.6456
CarcinogenicityNon-carcinogens0.8265
BiodegradationNot ready biodegradable0.996
Rat acute toxicity1.8756 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9907
hERG inhibition (predictor II)Non-inhibitor0.7221
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point190-194 °CPhysProp
logP0.70SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.296 mg/mLALOGPS
logP0.72ALOGPS
logP0.58ChemAxon
logS-3ALOGPS
pKa (Strongest Acidic)6.12ChemAxon
pKa (Strongest Basic)2.55ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area116.43 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity77.81 m3·mol-1ChemAxon
Polarizability30.01 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Dihydropteroate synthetase

Kind: protein

Organism: Plasmodium falciparum

Pharmacological action: yes

Components

Name UniProt ID Details
Dihydropteroate synthetase Q27738 Details

References:

  1. Raman J, Little F, Roper C, Kleinschmidt I, Cassam Y, Maharaj R, Barnes KI: Five years of large-scale dhfr and dhps mutation surveillance following the phased implementation of artesunate plus sulfadoxine-pyrimethamine in Maputo Province, Southern Mozambique. Am J Trop Med Hyg. 2010 May;82(5):788-94. Pubmed
  2. Zhang GQ, Guan YY, Zheng B, Wu S, Tang LH: Molecular assessment of Plasmodium falciparum resistance to antimalarial drugs in China. Trop Med Int Health. 2009 Oct;14(10):1266-71. Pubmed
  3. Lumb V, Das MK, Mittra P, Ahmed A, Kumar M, Kaur P, Dash AP, Singh SS, Sharma YD: Emergence of an unusual sulfadoxine-pyrimethamine resistance pattern and a novel K540N mutation in dihydropteroate synthetase in Plasmodium falciparum isolates obtained from Car Nicobar Island, India, after the 2004 Tsunami. J Infect Dis. 2009 Apr 1;199(7):1064-73. Pubmed

2. Bifunctional dihydrofolate reductase-thymidylate synthase

Kind: protein

Organism: Plasmodium falciparum (isolate K1 / Thailand)

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Bifunctional dihydrofolate reductase-thymidylate synthase P13922 Details

References:

  1. Eriksen J, Mwankusye S, Mduma S, Kitua A, Swedberg G, Tomson G, Gustafsson LL, Warsame M: Patterns of resistance and DHFR/DHPS genotypes of Plasmodium falciparum in rural Tanzania prior to the adoption of sulfadoxine-pyrimethamine as first-line treatment. Trans R Soc Trop Med Hyg. 2004 Jun;98(6):347-53. Pubmed
  2. Happi CT, Gbotosho GO, Folarin OA, Akinboye DO, Yusuf BO, Ebong OO, Sowunmi A, Kyle DE, Milhous W, Wirth DF, Oduola AM: Polymorphisms in Plasmodium falciparum dhfr and dhps genes and age related in vivo sulfadoxine-pyrimethamine resistance in malaria-infected patients from Nigeria. Acta Trop. 2005 Sep;95(3):183-93. Pubmed
  3. Fernandes NE, Cravo P, do Rosario VE: [Sulfadoxine-pyrimethamine resistance in Maputo, Mozambique: presence of mutations in the dhfr and dhps genes of Plasmodium falciparum] Rev Soc Bras Med Trop. 2007 Jul-Aug;40(4):447-50. Pubmed

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Drug created on June 30, 2007 08:21 / Updated on September 16, 2013 17:14