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Identification
NameSulfadoxine
Accession NumberDB01299
TypeSmall Molecule
GroupsApproved
DescriptionA long acting sulfonamide that is used, usually in combination with other drugs, for respiratory, urinary tract, and malarial infections. [PubChem]
Structure
Thumb
Synonyms
4-Sulfanilamido-5,6-dimethoxypyrimidine
Sulfadoxina
Sulfadoxine
Sulfadoxinum
Sulforthomidine
Sulphadoxine
Sulphormethoxine
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixtures
NameLabellerIngredients
Fansidar TabletsHoffmann La Roche Limited
SaltsNot Available
Categories
UNII88463U4SM5
CAS number2447-57-6
WeightAverage: 310.329
Monoisotopic: 310.073575646
Chemical FormulaC12H14N4O4S
InChI KeyInChIKey=PJSFRIWCGOHTNF-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.
Related Articles
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 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-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
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Tabletoral
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
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AcepromazineThe serum concentration of Acepromazine can be increased when it is combined with Sulfadoxine.
AlimemazineThe serum concentration of Alimemazine can be increased when it is combined with Sulfadoxine.
ArtemetherThe risk or severity of adverse effects can be increased when Artemether is combined with Sulfadoxine.
ChlorpromazineThe serum concentration of Chlorpromazine can be increased when it is combined with Sulfadoxine.
DapsoneThe risk or severity of adverse effects can be increased when Sulfadoxine is combined with Dapsone.
DexketoprofenThe risk or severity of adverse effects can be increased when Dexketoprofen is combined with Sulfadoxine.
FluphenazineThe serum concentration of Fluphenazine can be increased when it is combined with Sulfadoxine.
LumefantrineThe risk or severity of adverse effects can be increased when Sulfadoxine is combined with Lumefantrine.
MecamylamineThe risk or severity of adverse effects can be increased when Sulfadoxine is combined with Mecamylamine.
MesoridazineThe serum concentration of Mesoridazine can be increased when it is combined with Sulfadoxine.
MethotrimeprazineThe serum concentration of Methotrimeprazine can be increased when it is combined with Sulfadoxine.
Methylene blueThe serum concentration of Methylene blue can be increased when it is combined with Sulfadoxine.
MoricizineThe serum concentration of Moricizine can be increased when it is combined with Sulfadoxine.
PerphenazineThe serum concentration of Perphenazine can be increased when it is combined with Sulfadoxine.
ProchlorperazineThe serum concentration of Prochlorperazine can be increased when it is combined with Sulfadoxine.
PromazineThe serum concentration of Promazine can be increased when it is combined with Sulfadoxine.
PromethazineThe serum concentration of Promethazine can be increased when it is combined with Sulfadoxine.
ThiethylperazineThe serum concentration of Thiethylperazine can be increased when it is combined with Sulfadoxine.
ThioridazineThe serum concentration of Thioridazine can be increased when it is combined with Sulfadoxine.
TrifluoperazineThe serum concentration of Trifluoperazine can be increased when it is combined with Sulfadoxine.
TriflupromazineThe serum concentration of Triflupromazine can be increased when it is combined with Sulfadoxine.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Plasmodium falciparum
Pharmacological action
yes
General Function:
Dihydropteroate synthase activity
Specific Function:
Not Available
Gene Name:
Not Available
Uniprot ID:
Q27738
Molecular Weight:
43370.845 Da
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. doi: 10.4269/ajtmh.2010.09-0401. [PubMed:20439956 ]
  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. doi: 10.1111/j.1365-3156.2009.02342.x. [PubMed:19772548 ]
  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. doi: 10.1086/597206. [PubMed:19220141 ]
Kind
Protein
Organism
Plasmodium falciparum (isolate K1 / Thailand)
Pharmacological action
unknown
Actions
inhibitor
General Function:
Thymidylate synthase activity
Specific Function:
Bifunctional enzyme. Involved in de novo dTMP biosynthesis. Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, DNA precursor synthesis, and for the conversion of dUMP to dTMP.
Gene Name:
Not Available
Uniprot ID:
P13922
Molecular Weight:
71816.775 Da
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:15099990 ]
  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:16023986 ]
  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:17876469 ]
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Drug created on June 30, 2007 08:21 / Updated on August 17, 2016 12:23