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Record Information
Version2.0
Creation Date2009-07-03 22:07:24 UTC
Update Date2014-12-24 20:25:35 UTC
Accession NumberT3D2482
Identification
Common NameDapsone
ClassSmall Molecule
DescriptionA sulfone active against a wide range of bacteria but mainly employed for its actions against mycobacterium leprae. Its mechanism of action is probably similar to that of the sulfonamides which involves inhibition of folic acid synthesis in susceptible organisms. It is also used with pyrimethamine in the treatment of malaria. (From Martindale, The Extra Pharmacopoeia, 30th ed, p157-8)
Compound Type
  • Amine
  • Anti-Infective Agent
  • Anti-Inflammatory Agent
  • Antimalarial
  • Antimycobacterial
  • Drug
  • Folic Acid Antagonist
  • Leprostatic Agent
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
1,1'-Sulfonylbis(4-aminobenzene)
1,1'-Sulfonylbis[4-aminobenzene]
4,4'-Dapsone
4,4'-Diaminodiphenyl sulfone
4,4'-Diaminodiphenyl sulphone
4,4'-Diaminodiphenylsulfone
4,4'-Sulfonylbisaniline
4,4'-Sulfonylbisbenzenamine
4,4'-Sulfonylbisbenzeneamine
4,4'-Sulfonyldianilin
4,4'-sulfonyldianiline
4-(4-amino-Benzenesulfonyl)-phenylamine
4-(4-Aminophenylsulfonyl)aniline
4-(4-Aminophenylsulfonyl)benzenamine
4-Aminophenyl sulfone
Aczone
Bis(4-aminophenyl)sulfone
Bis(P-aminophenyl) sulfone
DADPS
Dapsona
DAPSONE
Dapsonum
DDS
DDS, pharmaceutical
DIAPHENYLSULFONE
P,P'-diaminodiphenyl sulfone
P,P-Sulphonylbisbenzamine
P,P-Sulphonylbisbenzenamine
P-Aminophenyl sulfone
Chemical FormulaC12H12N2O2S
Average Molecular Mass248.301 g/mol
Monoisotopic Mass248.062 g/mol
CAS Registry Number80-08-0
IUPAC Name4-(4-aminobenzenesulfonyl)aniline
Traditional Namedapsone
SMILESNC1=CC=C(C=C1)S(=O)(=O)C1=CC=C(N)C=C1
InChI IdentifierInChI=1S/C12H12N2O2S/c13-9-1-5-11(6-2-9)17(15,16)12-7-3-10(14)4-8-12/h1-8H,13-14H2
InChI KeyInChIKey=MQJKPEGWNLWLTK-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as benzenesulfonyl compounds. These are aromatic compounds containing a benzenesulfonyl group, which consists of a monocyclic benzene moiety that carries a sulfonyl group.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzenesulfonyl compounds
Direct ParentBenzenesulfonyl compounds
Alternative Parents
Substituents
  • Benzenesulfonyl group
  • Aniline or substituted anilines
  • Sulfonyl
  • Sulfone
  • Organic nitrogen compound
  • Organic oxygen compound
  • Organopnictogen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Primary amine
  • Organosulfur compound
  • Organonitrogen compound
  • Amine
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite or creamy white crystalline powder (3)
Experimental Properties
PropertyValue
Melting Point175.5°C
Boiling PointNot Available
Solubility380 mg/L (at 37°C)
LogP0.97
Predicted Properties
PropertyValueSource
Water Solubility0.28 g/LALOGPS
logP1.19ALOGPS
logP1.27ChemAxon
logS-2.9ALOGPS
pKa (Strongest Basic)2.39ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area86.18 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity68.99 m³·mol⁻¹ChemAxon
Polarizability25.05 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0564-9770000000-98d678eb70ae9cdbbfaaJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableJSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0a4i-5901100000-901603cf86087b4a4abbJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-0002-0190000000-7de0f1aeb77cf9b122f5JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-0002-0290000000-f1e61c46f1720875a177JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-0a4i-0920000000-ed66532a51b7d047462aJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-0a4l-3900000000-a1f636a2e557bc9b69a5JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-052f-9800000000-3557ad8246dc0a0aa05cJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0a4i-5910000000-0c8eb03605a271970f1dJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-052b-0590000000-a23b099ad5d2d3cd716dJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0a4i-1920000000-0260de715fec538fe8bbJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0a4l-5900000000-6ba41fa3598abafdb242JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-052f-9600000000-d2fe4c5ba425499ba98cJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-052f-9400000000-e29e2bdac763fc5e250bJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-066u-9200000000-71494cee2792628e6a0cJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-014i-9000000000-38433ad894a5e08f6ee0JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-014i-9000000000-e4782e47ceb05d1ffbdaJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-014i-9000000000-4ab9019e60b1718d1d29JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-0002-0190000000-d7cf0928be57fafd7ea4JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-0a4i-1930000000-09cf0e392eeef139f2b1JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-0a4l-8900000000-5da3a6d058cb14fc8300JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0002-0090000000-77f73a73b1a222285be3JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0002-0090000000-efb6858364a1d7c22428JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-004i-9430000000-d9c6fe280d40d0bc8dd6JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0002-0090000000-f3d8a4bdccbe1170ae6cJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0002-0090000000-ab2b74cff1f89de7c9a9JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9020000000-d4698e6b7c05ce3e71e6JSpectraViewer
MSMass Spectrum (Electron Ionization)splash10-052g-8930000000-c51783649020dadfb20fJSpectraViewer | MoNA
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
Toxicity Profile
Route of ExposureIngestion (15, 8); dermal (15, 8) ; eye contact (15, 8); inhalation (15, 8) Bioavailability is 70 to 80% following oral administration.
Mechanism of ToxicityDapsone acts against bacteria and protozoa in the same way as sulphonamides, that is by inhibiting the synthesis of dihydrofolic acid through competition with para-amino-benzoate for the active site of dihydropteroate synthetase. The anti-inflammatory action of the drug is unrelated to its antibacterial action and is still not fully understood.
MetabolismDapsone is slowly and nearly completely absporbed from GI tract, and distributed throughout the body. It is acetylated in the liver to monoacetyl and diacetyl derivatives. The major metabolite of dapsone is monoacetyldapsone. The rate of acetylation of dapsone is genetically determined and is subject to interindividual variation, although the rate is usually constant for each individual. The drug also is hydroxylated in the liver to hydroxylamine dapsone (NOH-DDS). NOH-DDS appears to be responsible for methemoglobinemia and hemolysis induced by the drug. The metabolites are excreted moslty in the urine. Only minor amounts of dapsone are excreted in feces. (4, 5). Route of Elimination: Renal Half Life: 28 hours (range 10-50 hours)
Toxicity ValuesLD50: 496 mg/kg (Oral, Mouse)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)3, not classifiable as to its carcinogenicity to humans. (14)
Uses/SourcesFor the treatment and management of leprosy and dermatitis herpetiformis. Dapsone is mainly employed for its actions against mycobacterium leprae. It is also used with pyrimethamine in the treatment of malaria, and of Pneumocystis carinii pneumonia (PCP) (1, 15).
Minimum Risk LevelNot Available
Health EffectsMethemoglobinemia and hemolysis are the main risks of acute intoxication. Hemolytic anemia, agranulocytosis, aplastic anemia and other blood dyscrasias may occur in chronic poisoning. Target organs are central and peripheral nervous systems, blood, liver and skin. Methemoglobinemia is the principal and constant feature of dapsone poisoning. Hemolytic anaemia and agranulocytosis may occur with the relatively low doses used for leprosy and malaria, whereas peripheral neuropathy and hepatitis are only observed with the higher doses used in the treatment of dermatitis herpetiformis. (16).
SymptomsOverdosage might be expected to produce nasal congestion, syncope, or hallucinations. Measures to support blood pressure should be taken if necessary.
TreatmentAdminister charcoal as a slurry following oral or parenteral exposure. (9)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00250
HMDB IDHMDB14395
PubChem Compound ID2955
ChEMBL IDCHEMBL1043
ChemSpider ID2849
KEGG IDC07666
UniProt IDNot Available
OMIM ID
ChEBI ID4325
BioCyc IDNot Available
CTD IDNot Available
Stitch IDDapsone
PDB IDNot Available
ACToR ID377
Wikipedia LinkDapsone
References
Synthesis Reference

Weijiard, J.and Messerly, J.P.; U.S. Patent 2,385,899; October 2,1945; assigned to Merck
& Co., Inc.

MSDSLink
General References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  2. Chu RC, Begley JA, Colligan PD, Hall CA: The methylcobalamin metabolism of cultured human fibroblasts. Metabolism. 1993 Mar;42(3):315-9. [8487649 ]
  3. Flanagan JN, Young MV, Persons KS, Wang L, Mathieu JS, Whitlatch LW, Holick MF, Chen TC: Vitamin D metabolism in human prostate cells: implications for prostate cancer chemoprevention by vitamin D. Anticancer Res. 2006 Jul-Aug;26(4A):2567-72. [16886665 ]
  4. Sakaki T, Kagawa N, Yamamoto K, Inouye K: Metabolism of vitamin D3 by cytochromes P450. Front Biosci. 2005 Jan 1;10:119-34. Print 2005 Jan 1. [15574355 ]
  5. Tokar EJ, Webber MM: Cholecalciferol (vitamin D3) inhibits growth and invasion by up-regulating nuclear receptors and 25-hydroxylase (CYP27A1) in human prostate cancer cells. Clin Exp Metastasis. 2005;22(3):275-84. [16158255 ]
  6. Malfara WR, Pereira CP, Santos AC, Queiroz RH: Effects of H(2)-receptor antagonists on dapsone-induced methaemoglobinaemia in rats. Pharmacol Res. 2002 Apr;45(4):269-73. [12030789 ]
  7. FLOCH H, GELARD AM: [Study of 4,4'-bis(ethylamino)-diphenylsulfone and of N-succinyl-4,4'diaminodiphenylsulfone administered intramuscularly in depot form]. Publ Inst Pasteur Guyane Fr Inini. 1954 Oct;15(343):1-7. [14377653 ]
  8. Lewis RJ (1996). Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold.
  9. Rumack BH (2009). POISINDEX(R) Information System. Englewood, CO: Micromedex, Inc. CCIS Volume 141, edition expires Aug, 2009.
  10. McEvoy GK (ed) (1998). American Hospital Formulary Service-Drug Information 19 98. Bethesda, MD: American Society of Health-System Pharmacists, Inc. (Plus Supplements).
  11. Hardman JG, Limbird LE, Molinoff PB, Ruddon RW, Goodman AG (eds) (1996). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill.
  12. Osol A, Hoover JE, et al. (eds) (1975). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co.
  13. Martindale, The Extra Pharmacopoeia, 30th ed, p157-8
  14. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
  15. Wikipedia. Dapsone. Last Updated 2 August 2009. [Link]
  16. International Programme on Chemical Safety (IPCS) INCHEM (1993). Poison Information Monograph for Dapsone. [Link]
  17. Drugs.com [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Nadph binding
Specific Function:
Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFRL1.
Gene Name:
DHFR
Uniprot ID:
P00374
Molecular Weight:
21452.61 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
General Function:
Serotonin receptor activity
Specific Function:
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that stimulate adenylate cyclase. It has a high affinity for tricyclic psychotropic drugs (By similarity). Controls pyramidal neurons migration during corticogenesis, through the regulation of CDK5 activity (By similarity). Is an activator of TOR signaling (PubMed:23027611).
Gene Name:
HTR6
Uniprot ID:
P50406
Molecular Weight:
46953.625 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.57 uMNVS_GPCR_h5HT6Novascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Monoamine transmembrane transporter activity
Specific Function:
Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name:
SLC6A3
Uniprot ID:
Q01959
Molecular Weight:
68494.255 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC504.25 uMNVS_TR_hDATNovascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]