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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
1,1'-Sulfonylbis[4-aminobenzene]Not AvailableNot Available
4-(4-amino-Benzenesulfonyl)-phenylamineNot AvailableNot Available
4-(4-Aminophenylsulfonyl)anilineNot AvailableNot Available
4-(4-Aminophenylsulfonyl)benzenamineNot AvailableNot Available
4-Aminophenyl sulfoneNot AvailableNot Available
4,4'-DapsoneNot AvailableNot Available
4,4'-Diaminodiphenyl sulfoneNot AvailableNot Available
4,4'-Diaminodiphenyl sulphoneNot AvailableNot Available
4,4'-DiaminodiphenylsulfoneNot AvailableNot Available
4,4'-SulfonylbisanilineNot AvailableNot Available
4,4'-SulfonylbisbenzenamineNot AvailableNot Available
4,4'-SulfonylbisbenzeneamineNot AvailableNot Available
4,4'-SulfonyldianilinNot AvailableNot Available
4,4'-sulfonyldianilineNot AvailableNot Available
Bis(4-aminophenyl)sulfoneNot AvailableNot Available
Bis(P-aminophenyl) sulfoneNot AvailableNot Available
DADPSNot AvailableNot Available
DapsonaNot AvailableNot Available
DAPSONENot AvailableNot Available
DapsonumNot AvailableNot Available
DDSNot AvailableNot Available
DIAPHENYLSULFONENot AvailableNot Available
P-Aminophenyl sulfoneNot AvailableNot Available
P,P-SulphonylbisbenzamineNot AvailableNot Available
P,P-SulphonylbisbenzenamineNot AvailableNot Available
P,P'-diaminodiphenyl sulfoneNot 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 KeyMQJKPEGWNLWLTK-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
Not Available
Nitroso-dapsoneDetails
Nitroso-dapsone
Not Available
Dapsone mercaptal intermediateDetails
Dapsone mercaptal intermediate
Not Available
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 °CNot Available
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 Solubility0.284ALOGPS
logP1.19ALOGPS
logP1.27ChemAxon
logS-2.9ALOGPS
pKa (Strongest Basic)2.39ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area86.18 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity68.99 m3·mol-1ChemAxon
Polarizability25.05 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectra1D NMR
References
Synthesis Reference

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

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.

Targets

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

Enzymes

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

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Drug created on June 13, 2005 07:24 / Updated on April 10, 2014 11:50