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IdentificationPharmacologyInteractionsReferencesTrialsEconomicsPropertiesSpectraTaxonomySulfadoxine
Identification
- Name
- Sulfadoxine
- Accession Number
- DB01299
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Description
A long acting sulfonamide that is used, usually in combination with other drugs, for respiratory, urinary tract, and malarial infections. [PubChem]
- Structure
Structure for Sulfadoxine (DB01299)
- Synonyms
- 4-Sulfanilamido-5,6-dimethoxypyrimidine
- Sulfadoxina
- Sulfadoxine
- Sulfadoxinum
- Sulforthomidine
- Sulphadoxine
- Sulphormethoxine
- External IDs
- J21.373J / RO-4-4393 / WR-4073
- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Fansidar Sulfadoxine (500 mg/1) + Pyrimethamine (25 mg/1) Tablet Oral Genentech, Inc. 1981-10-28 2012-04-18 US 
Fansidar Tablets Sulfadoxine (500 mg) + Pyrimethamine (25 mg) Tablet Oral Hoffmann La Roche 1989-12-31 2000-07-27 Canada 
- Categories
- Amides
- Amines
- Aniline Compounds
- Anti-Infective Agents
- Anti-Infective Agents, Urinary
- Antimalarials
- Antiparasitic Agents
- Antiprotozoals
- Genito Urinary System and Sex Hormones
- Gynecological Antiinfectives and Antiseptics
- Long-Acting Sulfonamides
- Renal Agents
- Sulfanilamides
- Sulfonamides
- Sulfones
- Sulfur Compounds
- UNII
- 88463U4SM5
- CAS number
- 2447-57-6
- Weight
- Average: 310.329
Monoisotopic: 310.073575646 - Chemical Formula
- C12H14N4O4S
- InChI Key
- 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
Pharmacology
- Indication
Sulfadoxine 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.
- Pharmacodynamics
Sulfadoxine 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 action
Sulfadoxine 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.
Target Actions Organism ADihydropteroate synthetase Not Available Plasmodium falciparum UBifunctional dihydrofolate reductase-thymidylate synthase inhibitorPlasmodium falciparum (isolate K1 / Thailand) - Absorption
- Not Available
- 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
- Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
Drug Interaction Acarbose The therapeutic efficacy of Acarbose can be increased when used in combination with Sulfadoxine. Acenocoumarol The therapeutic efficacy of Acenocoumarol can be increased when used in combination with Sulfadoxine. Acepromazine The serum concentration of Acepromazine can be increased when it is combined with Sulfadoxine. Aceprometazine The serum concentration of Aceprometazine can be increased when it is combined with Sulfadoxine. Alimemazine The risk or severity of QTc prolongation can be increased when Sulfadoxine is combined with Alimemazine. Artemether The risk or severity of QTc prolongation can be increased when Sulfadoxine is combined with Artemether. BL-1020 The serum concentration of BL-1020 can be increased when it is combined with Sulfadoxine. Botulinum Toxin Type A The risk or severity of adverse effects can be increased when Sulfadoxine is combined with Botulinum Toxin Type A. Botulinum Toxin Type B The risk or severity of adverse effects can be increased when Sulfadoxine is combined with Botulinum Toxin Type B. Bromocriptine The therapeutic efficacy of Bromocriptine can be increased when used in combination with Sulfadoxine. - Food Interactions
- Not Available
References
- General References
- Not Available
- External Links
- Human Metabolome Database
- HMDB0015413
- KEGG Drug
- D00580
- KEGG Compound
- C07630
- PubChem Compound
- 17134
- PubChem Substance
- 46507915
- ChemSpider
- 16218
- ChEBI
- 9329
- ChEMBL
- CHEMBL1539
- Therapeutic Targets Database
- DAP000638
- PharmGKB
- PA451540
- Wikipedia
- Sulfadoxine
- ATC Codes
- G01AE10 — Combinations of sulfonamides
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 1 Completed Treatment Autoimmune Diseases / Lymphoproliferative Disorders 1 2, 3 Completed Prevention Plasmodium Infections 1 2, 3 Completed Treatment Plasmodium Infections 1 3 Completed Prevention Plasmodium Infections 1 3 Completed Treatment Human Immunodeficiency Virus (HIV) Infections / Pneumonia, Pneumocystis Carinii 1 3 Completed Treatment Plasmodium Infections 1 3 Recruiting Prevention Plasmodium Infections / Pregnancy 1 3 Terminated Treatment Plasmodium Infections 1 3 Withdrawn Treatment Plasmodium Falciparum Malaria 1 4 Completed Prevention Plasmodium Infections 1 4 Completed Treatment Plasmodium Falciparum Malaria / Plasmodium Infections 1 4 Recruiting Prevention Malaria caused by Plasmodium falciparum 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- F Hoffmann La Roche Ltd.
- F Hoffmann-La Roche Ltd.
- Dosage forms
Form Route Strength Tablet Oral - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 190-194 °C PhysProp logP 0.70 SANGSTER (1994) - Predicted Properties
Property Value Source Water Solubility 0.296 mg/mL ALOGPS logP 0.72 ALOGPS logP 0.58 ChemAxon logS -3 ALOGPS pKa (Strongest Acidic) 6.12 ChemAxon pKa (Strongest Basic) 2.55 ChemAxon Physiological Charge -1 ChemAxon Hydrogen Acceptor Count 7 ChemAxon Hydrogen Donor Count 2 ChemAxon Polar Surface Area 116.43 Å2 ChemAxon Rotatable Bond Count 4 ChemAxon Refractivity 77.81 m3·mol-1 ChemAxon Polarizability 30.01 Å3 ChemAxon Number of Rings 2 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter Yes ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET features
Property Value Probability Human Intestinal Absorption + 0.9602 Blood Brain Barrier - 0.5345 Caco-2 permeable - 0.59 P-glycoprotein substrate Non-substrate 0.8126 P-glycoprotein inhibitor I Non-inhibitor 0.832 P-glycoprotein inhibitor II Non-inhibitor 0.8892 Renal organic cation transporter Non-inhibitor 0.9164 CYP450 2C9 substrate Non-substrate 0.693 CYP450 2D6 substrate Non-substrate 0.9116 CYP450 3A4 substrate Non-substrate 0.6464 CYP450 1A2 substrate Non-inhibitor 0.9045 CYP450 2C9 inhibitor Non-inhibitor 0.9071 CYP450 2D6 inhibitor Non-inhibitor 0.9231 CYP450 2C19 inhibitor Non-inhibitor 0.9026 CYP450 3A4 inhibitor Non-inhibitor 0.8703 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.6052 Ames test Non AMES toxic 0.6456 Carcinogenicity Non-carcinogens 0.8265 Biodegradation Not ready biodegradable 0.996 Rat acute toxicity 1.8756 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9907 hERG inhibition (predictor II) Non-inhibitor 0.7221
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available LC-MS/MS Spectrum - LC-ESI-qTof , Positive LC-MS/MS Not Available LC-MS/MS Spectrum - LC-ESI-QTOF , positive LC-MS/MS splash10-0a4i-2901000000-8862dd6e93b57f07349b MS/MS Spectrum - , positive LC-MS/MS splash10-0a4i-3910000000-fbde0b31ef009afef44d
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 / Alkyl aryl ethers / Pyrimidines and pyrimidine derivatives / Organosulfonamides / Imidolactams / Heteroaromatic compounds / Aminosulfonyl compounds / Azacyclic compounds / Primary amines show 3 more
- Substituents
- Aminobenzenesulfonamide / Benzenesulfonyl group / Aniline or substituted anilines / Alkyl aryl ether / Pyrimidine / Organosulfonic acid amide / Imidolactam / Organic sulfonic acid or derivatives / Organosulfonic acid or derivatives / Sulfonyl show 16 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- sulfonamide, pyrimidines (CHEBI:9329)
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
- Uniprot Name
- Dihydropteroate synthetase
- Molecular Weight
- 43370.845 Da
References
- 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]
- 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]
- 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 f...
- Gene Name
- Not Available
- Uniprot ID
- P13922
- Uniprot Name
- Bifunctional dihydrofolate reductase-thymidylate synthase
- Molecular Weight
- 71816.775 Da
References
- 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]
- 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]
- 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]
Drug created on June 30, 2007 08:21 / Updated on August 02, 2018 04:34