Welcome to DrugBank 4.0! If you prefer, you can still go back to version 3.0.
Identification
NameDapsone
Accession NumberDB00250  (APRD00345)
Typesmall molecule
Groupsapproved, investigational
Description

A 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)

Structure
Thumb
Synonyms
SynonymLanguageCode
1,1'-Sulfonylbis[4-aminobenzene]Not AvailableNot Available
4,4'-Diaminodiphenyl sulfoneNot AvailableNot Available
4,4'-Diaminodiphenyl sulphoneNot AvailableNot Available
4,4'-DiaminodiphenylsulfoneNot AvailableNot Available
4,4'-SulfonylbisbenzeneamineNot AvailableNot Available
4,4'-SulfonyldianilinNot AvailableNot Available
4,4'-sulfonyldianilineNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
AczoneAllergan
Brand mixturesNot Available
Categories
CAS number80-08-0
WeightAverage: 248.301
Monoisotopic: 248.061948328
Chemical FormulaC12H12N2O2S
InChI KeyInChIKey=MQJKPEGWNLWLTK-UHFFFAOYSA-N
InChI
InChI=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
IUPAC Name
4-[(4-aminobenzene)sulfonyl]aniline
SMILES
NC1=CC=C(C=C1)S(=O)(=O)C1=CC=C(N)C=C1
Mass Specshow(9.27 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassAnilines
Direct parentSulfonylanilines
Alternative parentsPrimary Aromatic Amines; Sulfones; Sulfoxides; Polyamines
Substituentsprimary aromatic amine; sulfone; sulfonyl; sulfoxide; polyamine; amine; primary amine; organonitrogen compound
Classification descriptionThis compound belongs to the sulfonylanilines. These are compounds containing an aniline moiety which bears a sulfonyl group at ring position 4.
Pharmacology
IndicationFor the treatment and management of leprosy and dermatitis herpetiformis.
PharmacodynamicsDapsone is a sulfone with anti-inflammatory immunosuppressive properties as well as antibacterial and antibiotic properties. Dapsone is the principal drug in a multidrug regimen recommended by the World Health Organization for the treatment of leprosy. As an anti-infective agent, it is also used for treating malaria and, recently, for Pneumocystic carinii pneumonia in AIDS patients. Dapsone is absorbed rapidly and nearly completely from the gastrointestinal tract. Dapsone is distributed throughout total body water and is present in all tissues. However, it tends to be retained in skin and muscle and especially in the liver and kidney: traces of the drug are present in these organs up to 3 weeks after therapy cessation.
Mechanism of actionDapsone 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.
AbsorptionBioavailability is 70 to 80% following oral administration.
Volume of distributionNot Available
Protein binding70 to 90%
Metabolism

Hepatic, mostly CYP2E1-mediated.

SubstrateEnzymesProduct
Dapsone
dapsone hydroxylamineDetails
Dapsone
N-AcetyldapsoneDetails
dapsone hydroxylamine
    Nitroso-dapsoneDetails
    Nitroso-dapsone
      Dapsone mercaptal intermediateDetails
      Dapsone mercaptal intermediate
        Dapsone GSH conjugateDetails
        Route of eliminationRenal
        Half life28 hours (range 10-50 hours)
        ClearanceNot Available
        ToxicityOverdosage might be expected to produce nasal congestion, syncope, or hallucinations. Measures to support blood pressure should be taken if necessary.
        Affected organisms
        • Mycobacteria
        PathwaysNot Available
        SNP Mediated EffectsNot Available
        SNP Mediated Adverse Drug ReactionsNot Available
        ADMET
        Predicted ADMET features
        Property Value Probability
        Human Intestinal Absorption + 0.8476
        Blood Brain Barrier + 0.9705
        Caco-2 permeable + 0.5879
        P-glycoprotein substrate Non-substrate 0.8699
        P-glycoprotein inhibitor I Non-inhibitor 0.9311
        P-glycoprotein inhibitor II Non-inhibitor 0.9572
        Renal organic cation transporter Non-inhibitor 0.8739
        CYP450 2C9 substrate Non-substrate 0.7416
        CYP450 2D6 substrate Substrate 0.86
        CYP450 3A4 substrate Non-substrate 0.7175
        CYP450 1A2 substrate Non-inhibitor 0.9046
        CYP450 2C9 substrate Non-inhibitor 0.8955
        CYP450 2D6 substrate Non-inhibitor 0.9231
        CYP450 2C19 substrate Non-inhibitor 0.9026
        CYP450 3A4 substrate Inhibitor 0.6127
        CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.556
        Ames test Non AMES toxic 0.9132
        Carcinogenicity Non-carcinogens 0.5795
        Biodegradation Not ready biodegradable 0.9778
        Rat acute toxicity 2.3635 LD50, mol/kg Not applicable
        hERG inhibition (predictor I) Weak inhibitor 0.9859
        hERG inhibition (predictor II) Non-inhibitor 0.864
        Pharmacoeconomics
        Manufacturers
        • Jacobus pharmaceutical co
        Packagers
        Dosage forms
        FormRouteStrength
        TabletOral
        Prices
        Unit descriptionCostUnit
        Dapsone 30 100 mg tablet Box42.99USDbox
        Dapsone 30 25 mg tablet Box35.99USDbox
        Aczone 5% gel5.52USDg
        Dapsone powder5.38USDg
        Dapsone 100 mg tablet0.86USDtablet
        Dapsone 25 mg tablet0.2USDtablet
        DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
        Patents
        CountryPatent NumberApprovedExpires (estimated)
        Canada22654612004-11-302017-09-10
        Properties
        Statesolid
        Experimental Properties
        PropertyValueSource
        melting point175.5 °CPhysProp
        water solubility380 mg/L (at 37 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
        logP0.97HANSCH,C ET AL. (1995)
        logS-2.82ADME Research, USCD
        pKa2.41PERRIN,DD (1965)
        Predicted Properties
        PropertyValueSource
        water solubility2.84e-01 g/lALOGPS
        logP1.19ALOGPS
        logP1.27ChemAxon
        logS-2.9ALOGPS
        pKa (strongest basic)2.39ChemAxon
        physiological charge0ChemAxon
        hydrogen acceptor count4ChemAxon
        hydrogen donor count2ChemAxon
        polar surface area86.18ChemAxon
        rotatable bond count2ChemAxon
        refractivity68.99ChemAxon
        polarizability25.05ChemAxon
        number of rings2ChemAxon
        bioavailability1ChemAxon
        rule of fiveYesChemAxon
        Ghose filterYesChemAxon
        Veber's ruleNoChemAxon
        MDDR-like ruleNoChemAxon
        Spectra
        SpectraNot Available
        References
        Synthesis ReferenceNot Available
        General ReferenceNot Available
        External Links
        ResourceLink
        KEGG DrugD00592
        KEGG CompoundC07666
        PubChem Compound2955
        PubChem Substance46505300
        ChemSpider2849
        BindingDB50029764
        ChEBI4325
        ChEMBLCHEMBL1043
        Therapeutic Targets DatabaseDAP000637
        PharmGKBPA449211
        Drug Product Database2041510
        RxListhttp://www.rxlist.com/cgi/generic/dapsone.htm
        Drugs.comhttp://www.drugs.com/cdi/dapsone.html
        WikipediaDapsone
        ATC CodesD10AX05J04BA02
        AHFS Codes
        • 08:16.92
        PDB EntriesNot Available
        FDA labelshow(515 KB)
        MSDSshow(53.5 KB)
        Interactions
        Drug Interactions
        Drug
        AluminiumFormation of non-absorbable complexes
        CalciumFormation of non-absorbable complexes
        LumefantrineConcomitant therapy may increase the risk of adverse hemolytic reactions. Monitor patients closely for symptoms of hemolytic reactions during concomitant therapy. Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, methoglobulin reductase deficiency or hemoglobin M are at higher risk of experiencing hemolytic reactions.
        MagnesiumFormation of non-absorbable complexes
        Magnesium oxideFormation of non-absorbable complexes
        RifabutinDecreased levels of dapsone
        RifampicinDecreased levels of dapsone
        TelithromycinTelithromycin may reduce clearance of Dapsone. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Dapsone if Telithromycin is initiated, discontinued or dose changed.
        TolbutamideTolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Dapsone. Consider alternate therapy or monitor for changes in Dapsone therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.
        TrimethoprimIncreased toxicity of both products
        VoriconazoleVoriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of dapsone by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of dapsone if voriconazole is initiated, discontinued or dose changed.
        Food Interactions
        • Take without regard to meals.

        1. Inactive dihydropteroate synthase 2

        Kind: protein

        Organism: Mycobacterium leprae (strain TN)

        Pharmacological action: yes

        Actions: inhibitor

        Components

        Name UniProt ID Details
        Inactive dihydropteroate synthase 2 P0C0X2 Details

        References:

        1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
        2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
        3. Gillis TP, Williams DL: Dapsone resistance does not appear to be associated with a mutation in the dihydropteroate synthase-2 gene of Mycobacterium leprae. Indian J Lepr. 1999 Jan-Mar;71(1):11-8. Pubmed
        4. Williams DL, Spring L, Harris E, Roche P, Gillis TP: Dihydropteroate synthase of Mycobacterium leprae and dapsone resistance. Antimicrob Agents Chemother. 2000 Jun;44(6):1530-7. Pubmed
        5. Gengenbacher M, Xu T, Niyomrattanakit P, Spraggon G, Dick T: Biochemical and structural characterization of the putative dihydropteroate synthase ortholog Rv1207 of Mycobacterium tuberculosis. FEMS Microbiol Lett. 2008 Oct;287(1):128-35. Epub 2008 Aug 1. Pubmed

        2. Dihydropteroate synthase 1

        Kind: protein

        Organism: Mycobacterium leprae (strain TN)

        Pharmacological action: yes

        Actions: inhibitor

        Components

        Name UniProt ID Details
        Dihydropteroate synthase 1 P0C0X1 Details

        References:

        1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
        2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
        3. Cambau E, Carthagena L, Chauffour A, Ji B, Jarlier V: Dihydropteroate synthase mutations in the folP1 gene predict dapsone resistance in relapsed cases of leprosy. Clin Infect Dis. 2006 Jan 15;42(2):238-41. Epub 2005 Dec 12. Pubmed
        4. Lee SB, Kim SK, Kang TJ, Chae GT, Chun JH, Shin HK, Kim JP, Ko YH, Kim NH: The prevalence of folP1 mutations associated with clinical resistance to dapsone, in Mycobacterium leprae isolates from South Korea. Ann Trop Med Parasitol. 2001 Jun;95(4):429-32. Pubmed
        5. Williams DL, Spring L, Harris E, Roche P, Gillis TP: Dihydropteroate synthase of Mycobacterium leprae and dapsone resistance. Antimicrob Agents Chemother. 2000 Jun;44(6):1530-7. Pubmed
        6. Gengenbacher M, Xu T, Niyomrattanakit P, Spraggon G, Dick T: Biochemical and structural characterization of the putative dihydropteroate synthase ortholog Rv1207 of Mycobacterium tuberculosis. FEMS Microbiol Lett. 2008 Oct;287(1):128-35. Epub 2008 Aug 1. Pubmed

        1. Cytochrome P450 3A5

        Kind: protein

        Organism: Human

        Pharmacological action: unknown

        Actions: substrate

        Components

        Name UniProt ID Details
        Cytochrome P450 3A5 P20815 Details

        References:

        1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

        2. Cytochrome P450 3A4

        Kind: protein

        Organism: Human

        Pharmacological action: unknown

        Actions: substrate

        Components

        Name UniProt ID Details
        Cytochrome P450 3A4 P08684 Details

        References:

        1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
        2. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
        3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
        4. Ekins S, Bravi G, Wikel JH, Wrighton SA: Three-dimensional-quantitative structure activity relationship analysis of cytochrome P-450 3A4 substrates. J Pharmacol Exp Ther. 1999 Oct;291(1):424-33. Pubmed

        3. Dimethylaniline monooxygenase [N-oxide-forming] 3

        Kind: protein

        Organism: Human

        Pharmacological action: unknown

        Actions: substrate

        Components

        Name UniProt ID Details
        Dimethylaniline monooxygenase [N-oxide-forming] 3 P31513 Details

        References:

        1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed

        4. Prostaglandin G/H synthase 1

        Kind: protein

        Organism: Human

        Pharmacological action: unknown

        Actions: substrate

        Components

        Name UniProt ID Details
        Prostaglandin G/H synthase 1 P23219 Details

        References:

        1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed

        5. Prostaglandin G/H synthase 2

        Kind: protein

        Organism: Human

        Pharmacological action: unknown

        Actions: substrate

        Components

        Name UniProt ID Details
        Prostaglandin G/H synthase 2 P35354 Details

        References:

        1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed

        6. Cytochrome P450 2C8

        Kind: protein

        Organism: Human

        Pharmacological action: unknown

        Actions: substrate

        Components

        Name UniProt ID Details
        Cytochrome P450 2C8 P10632 Details

        References:

        1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
        2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

        7. Cytochrome P450 2C19

        Kind: protein

        Organism: Human

        Pharmacological action: unknown

        Actions: substrate

        Components

        Name UniProt ID Details
        Cytochrome P450 2C19 P33261 Details

        References:

        1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
        2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

        8. Arylamine N-acetyltransferase 2

        Kind: protein

        Organism: Human

        Pharmacological action: unknown

        Actions: substrate

        Components

        Name UniProt ID Details
        Arylamine N-acetyltransferase 2 P11245 Details

        References:

        1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed

        9. Cytochrome P450 2C9

        Kind: protein

        Organism: Human

        Pharmacological action: unknown

        Actions: substrate inducer

        Components

        Name UniProt ID Details
        Cytochrome P450 2C9 P11712 Details

        References:

        1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
        2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
        3. Winter HR, Wang Y, Unadkat JD: CYP2C8/9 mediate dapsone N-hydroxylation at clinical concentrations of dapsone. Drug Metab Dispos. 2000 Aug;28(8):865-8. Pubmed

        10. Cytochrome P450 3A7

        Kind: protein

        Organism: Human

        Pharmacological action: unknown

        Actions: substrate

        Components

        Name UniProt ID Details
        Cytochrome P450 3A7 P24462 Details

        References:

        1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

        11. Cytochrome P450 2E1

        Kind: protein

        Organism: Human

        Pharmacological action: unknown

        Actions: substrate

        Components

        Name UniProt ID Details
        Cytochrome P450 2E1 P05181 Details

        References:

        1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
        2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

        12. Myeloperoxidase

        Kind: protein

        Organism: Human

        Pharmacological action: unknown

        Actions: substrate

        Components

        Name UniProt ID Details
        Myeloperoxidase P05164 Details

        References:

        1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed

        13. Cytochrome P450 2C18

        Kind: protein

        Organism: Human

        Pharmacological action: unknown

        Actions: substrate

        Components

        Name UniProt ID Details
        Cytochrome P450 2C18 P33260 Details

        References:

        1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

        Comments
        Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:08