Identification

Name
Anthralin
Accession Number
DB11157
Type
Small Molecule
Groups
Approved
Description

Anthralin (1,8‐dihydroxy‐9anthrone, dithranol) is an older anti-psoriatic agent that was first synthesized as a derivative of chrysarobin, obtained from the araroba tree in Brazil over 100 years ago. Adverse effects of anthralin include irritation and discoloration of the skin [2].

This specific property of the molecule inspired workers to study details of its pharmacology. It is important to consider that the drug is relatively innocuous, yet effective, and systemic side effects have not been observed with this anthralin, in contrast to a wide variety of systemic and topical therapies for psoriasis [9].

Anthralin is also known as dithranol. It is a main active ingredient in topical skin formulations for the treatment of psoriasis. Various formulations of the drug are available, including solutions, foams, and shampoos [13]. The chemical structure of anthralin allows for dual solubility, permitting the compound to be absorbed well through the epidermis [1].

Anthralin has also been studied in the treatment of warts, showing promising results [3]. Salicylic acid is frequently added to anthralin to augment the stability of anthralin and to increase its penetration and efficacy [13].

Structure
Thumb
Synonyms
  • Dithranol
  • Ditranol
External IDs
NSC-43970 / NSC-629313
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Anthraforte 1 Ointment 1%Ointment1 %TopicalMedican Technologies Inc.1984-12-312014-09-02Canada
Anthraforte 2 Ointment 2%Ointment2 %TopicalMedican Technologies Inc.1984-12-312014-09-02Canada
Anthranol Cream 0.1%Cream0.1 %TopicalMedican Technologies Inc.1982-12-312014-09-02Canada
Anthranol Cream 0.2%Cream0.2 %TopicalMedican Technologies Inc.1982-12-312014-09-02Canada
Anthranol Cream 0.4%Cream0.4 %TopicalMedican Technologies Inc.1982-12-312000-06-30Canada
Anthrascalp Lotion 0.4%Lotion0.4 %TopicalMedican Technologies Inc.1987-12-312014-09-02Canada
Micanol 3% CreamCream3 %TopicalCanderm G.P.1998-09-012004-07-30Canada
Micanol CreamCream1 %TopicalCanderm G.P.1998-05-062004-07-30Canada
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Dritho-creme HpAnthralin (1 g/100g)CreamTopicalSummers Laboratories2013-01-01Not applicableUs
ZithranolAnthralin (1 g/100g)ShampooTopicalElorac, Inc.2012-03-05Not applicableUs
Zithranol-RRAnthralin (.012 g/1g)CreamTopicalElorac, Inc.2009-07-09Not applicableUs
Categories
UNII
U8CJK0JH5M
CAS number
1143-38-0
Weight
Average: 226.231
Monoisotopic: 226.062994182
Chemical Formula
C14H10O3
InChI Key
NUZWLKWWNNJHPT-UHFFFAOYSA-N
InChI
InChI=1S/C14H10O3/c15-10-5-1-3-8-7-9-4-2-6-11(16)13(9)14(17)12(8)10/h1-6,15-16H,7H2
IUPAC Name
1,8-dihydroxy-9,10-dihydroanthracen-9-one
SMILES
OC1=CC=CC2=C1C(=O)C1=C(O)C=CC=C1C2

Pharmacology

Indication

Stable plaque psoriasis of the skin and scalp [8].

It is also used topically in the management of psoriasis, dermatoses, and alopecia areata. Anthralin is also used in biomedical research due to its effect on EGFR autophosphorylation [10].

Pharmacodynamics

Anthralin is a natural anthraquinone derivative, anti-psoriatic and anti-inflammatory agent. It controls skin growth by reducing the synthesis of DNA and the mitotic activity in the hyperplastic epidermis, normalizing the rate of cell proliferation and keratinization [10].

Mechanism of action

Anthralin inhibits the proliferation of keratinocytes (epidermal skin cells), prevents the action of T-cells, and promotes cell differentiation, likely through mitochondrial dysfunction. In addition, the production of free radicals may contribute to its anti-psoriatic effect [13]. In vitro studies demonstrate that anthralin prolongs the prophase component of mitosis for keratinocytes and leukocytes [7]. Prophase is the first step of mitosis, the process separating the duplicated genetic material carried in the nucleus of a parent cell into two identical daughter cells [14]. In vivo studies demonstrate that anthralin blocks DNA synthesis and can increase the release of reactive oxygen species [7].

Anthralin is believed to normalize the rate of epidermal cell proliferation and keratinization by reducing the mitotic activity of the epidermal hyperplasia in psoriasis [13].

Anti-proliferative and anti-inflammatory effects of anthralin have been demonstrated on both psoriatic and healthy skin. The anti-proliferative effects of anthralin are believed to result from both an inhibition of DNA synthesis as well as from strong reducing properties. The effectiveness of anthralin as an anti-psoriatic agent is partly owed to its ability to promote lipid peroxidation and reduce the concentration of endothelial adhesion molecules, which are found to be elevated in psoriatic patients [8], [13].

Recent studies suggest that its ability to prevent T-lymphocyte activation and normalize keratinocyte differentiation may occur by a direct effect on mitochondria [4].

TargetActionsOrganism
AKeratin, type II cytoskeletal 2 epidermal
antagonist
Human
UC-Jun-amino-terminal kinase-interacting protein 1
agonist
Human
AKeratin, type I cytoskeletal 12
antagonist
Human
Absorption

Anthralin penetrates damaged skin and psoriatic lesions faster and to a greater extent than normal skin, likely due to increased vascularity of psoriatic lesions [7].

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Anthralin is administered topically. Although the extent of systemic absorption after topical application has not been determined, no traces of anthraquinone metabolites were detected in the urine of treated subjects in a limited clinical study of anthralin cream [7], [8].

Anthralin does not inhibit hepatic microsomal enzyme activity [8].

Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

Some mild adverse effects include alterations in nail coloring, hair coloring, increase in photosensitivity, and skin irritation [8].

The most common side effects of anthralin are skin irritation and staining of nearby skin, nails, clothing, and other objects that come in contact with the treated patient. The incidence of irritation of psoriatic/surrounding healthy skin is higher in patients who leave anthralin on the skin without rinsing than in those who use short-contact therapy of 2 hours or less, followed by rinsing [12].

If the psoriatic plaques are well circumscribed, the surrounding normal skin may be protected by the use of a coating agent such as zinc oxide ointment. Anthralin should be applied cautiously to the face and intertriginous areas due to the risk of severe skin irritation [13].

There is no current evidence of any long-term anthralin toxicity related either to skin exposure or to systemic issues [12]. Some long-term studies in mice have demonstrated anthralin to be tumorigenic in mouse skin. This carcinogenic potential has not been thoroughly evaluated. Tumorigenic and carcinogenic effects of anthralin have not been observed in humans at this time [7]. Anthralin is classified as FDA pregnancy risk category C drug [13]. It is not known if anthralin can cause fetal harm when administered during gestation. Because of the lack of evidential human data, anthralin should be used during pregnancy only when clearly required [8].

Affected organisms
  • Humans
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Ashton RE, Andre P, Lowe NJ, Whitefield M: Anthralin: historical and current perspectives. J Am Acad Dermatol. 1983 Aug;9(2):173-92. [PubMed:6309924]
  2. Sehgal VN, Verma P, Khurana A: Anthralin/dithranol in dermatology. Int J Dermatol. 2014 Oct;53(10):e449-60. doi: 10.1111/j.1365-4632.2012.05611.x. Epub 2014 Sep 10. [PubMed:25208745]
  3. Flindt-Hansen H, Tikjob G, Brandrup F: Wart treatment with anthralin. Acta Derm Venereol. 1984;64(2):177-9. [PubMed:6203313]
  4. McGill A, Frank A, Emmett N, Turnbull DM, Birch-Machin MA, Reynolds NJ: The anti-psoriatic drug anthralin accumulates in keratinocyte mitochondria, dissipates mitochondrial membrane potential, and induces apoptosis through a pathway dependent on respiratory competent mitochondria. FASEB J. 2005 Jun;19(8):1012-4. doi: 10.1096/fj.04-2664fje. Epub 2005 Mar 31. [PubMed:15802490]
  5. Diezel W, Meffert H, Sonnichsen N: [Study on the mode of action of dithranol: increased lipid peroxidation and enzyme inhibition]. Dermatologica. 1975;150(3):154-62. [PubMed:125665]
  6. Peus D, Beyerle A, Rittner HL, Pott M, Meves A, Weyand C, Pittelkow MR: Anti-psoriatic drug anthralin activates JNK via lipid peroxidation: mononuclear cells are more sensitive than keratinocytes. J Invest Dermatol. 2000 Apr;114(4):688-92. doi: 10.1046/j.1523-1747.2000.00934.x. [PubMed:10733674]
  7. Anthralin [Link]
  8. Zithranol, PDR [Link]
  9. Anthralin/dithranol in dermatology [Link]
  10. PubChem, Anthralin [Link]
  11. Zithranol-RR [Link]
  12. American Academy of Dermatology Recommendations [Link]
  13. NIH.gov Topical Therapies in psoriasis [Link]
  14. Prophase Definition [Link]
External Links
KEGG Compound
C06831
PubChem Compound
2202
PubChem Substance
347827926
ChemSpider
2117
BindingDB
50041802
ChEBI
37510
ChEMBL
CHEMBL46469
Wikipedia
Dithranol
ATC Codes
D05AC51 — Dithranol, combinationsD05AC01 — Dithranol
MSDS
Download (47.8 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
OintmentTopical1 %
OintmentTopical2 %
CreamTopical0.1 %
CreamTopical0.2 %
CreamTopical0.4 %
LotionTopical0.4 %
CreamTopical1 g/100g
CreamTopical3 %
CreamTopical1 %
ShampooTopical1 g/100g
CreamTopical.012 g/1g
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)178-182 °CMSDS
water solubilitynot soluble in waterMSDS
Predicted Properties
PropertyValueSource
Water Solubility0.184 mg/mLALOGPS
logP2.73ALOGPS
logP4.24ChemAxon
logS-3.1ALOGPS
pKa (Strongest Acidic)8.47ChemAxon
pKa (Strongest Basic)-5.6ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area57.53 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity64.27 m3·mol-1ChemAxon
Polarizability23.12 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Mass Spectrum (Electron Ionization)MSsplash10-004i-3790000000-74ab4aae2d6ceb313831
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
1H NMR Spectrum1D NMRNot Applicable
13C NMR Spectrum1D NMRNot Applicable

Taxonomy

Description
This compound belongs to the class of organic compounds known as anthracenes. These are organic compounds containing a system of three linearly fused benzene rings.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Anthracenes
Sub Class
Not Available
Direct Parent
Anthracenes
Alternative Parents
Aryl ketones / 1-hydroxy-4-unsubstituted benzenoids / 1-hydroxy-2-unsubstituted benzenoids / Vinylogous acids / Organic oxides / Hydrocarbon derivatives
Substituents
Anthracene / Aryl ketone / 1-hydroxy-4-unsubstituted benzenoid / 1-hydroxy-2-unsubstituted benzenoid / Vinylogous acid / Ketone / Organic oxygen compound / Organic oxide / Hydrocarbon derivative / Organooxygen compound
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
anthracenes (CHEBI:37510)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Probably contributes to terminal cornification. Associated with keratinocyte activation, proliferation and keratinization.
Specific Function
Cytoskeletal protein binding
Gene Name
KRT2
Uniprot ID
P35908
Uniprot Name
Keratin, type II cytoskeletal 2 epidermal
Molecular Weight
65432.65 Da
References
  1. McGill A, Frank A, Emmett N, Turnbull DM, Birch-Machin MA, Reynolds NJ: The anti-psoriatic drug anthralin accumulates in keratinocyte mitochondria, dissipates mitochondrial membrane potential, and induces apoptosis through a pathway dependent on respiratory competent mitochondria. FASEB J. 2005 Jun;19(8):1012-4. doi: 10.1096/fj.04-2664fje. Epub 2005 Mar 31. [PubMed:15802490]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Protein kinase inhibitor activity
Specific Function
The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module. Req...
Gene Name
MAPK8IP1
Uniprot ID
Q9UQF2
Uniprot Name
C-Jun-amino-terminal kinase-interacting protein 1
Molecular Weight
77523.56 Da
References
  1. Peus D, Beyerle A, Rittner HL, Pott M, Meves A, Weyand C, Pittelkow MR: Anti-psoriatic drug anthralin activates JNK via lipid peroxidation: mononuclear cells are more sensitive than keratinocytes. J Invest Dermatol. 2000 Apr;114(4):688-92. doi: 10.1046/j.1523-1747.2000.00934.x. [PubMed:10733674]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Structural molecule activity
Specific Function
May play a unique role in maintaining the normal corneal epithelial function. Together with KRT3, essential for the maintenance of corneal epithelium integrity (By similarity).
Gene Name
KRT12
Uniprot ID
Q99456
Uniprot Name
Keratin, type I cytoskeletal 12
Molecular Weight
53510.935 Da
References
  1. Anthralin/dithranol in dermatology [Link]

Drug created on December 03, 2015 09:51 / Updated on November 05, 2018 17:49