On the Stability of Some Antipsoriatic Active Anthralin (Dithranol) Derivatives

Schaltegger, A.; Bloch, Ursus; Krebs, A

doi:10.1159/000249961

Cited by 8 publications

(2 citation statements)

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“…Although 10-acyl analogues of anthralin have been shown to be active,I2 they are also thought to be hydrolysed to anthralin in the skin. 13 Generation of radicals from anthralin for analytical purposes has been achieved by several methods including phot~lysis,'~ heat-accelerated oxidation in a pure ~olvent,'~ peroxidation of lipids in an abundant oxygen supply ' or with alkaline agents and topical application to the However, in order to obtain high resolution ESR spectra optimal conditions are required. The present study describes the radicals generated in degassed xylene by photolysis and by thermolysis of anthralin and several of its analogues.…”

Section: Experiments A1mentioning

confidence: 99%

An ESR study of thermal and photo-induced formation of radicals from anthralin and acylated derivatives

Lambelet¹,

Prior²,

Löliger³

et al. 1990

J. Chem. Soc., Perkin Trans. 2

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Section: Experiments A1mentioning

confidence: 99%

An ESR study of thermal and photo-induced formation of radicals from anthralin and acylated derivatives

Lambelet¹,

Prior²,

Löliger³

et al. 1990

J. Chem. Soc., Perkin Trans. 2

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“…1). However, 3 is a so-called phenylogic P-diketone, which hydrolizes to dithranol in aqueous media, as we have recently demonstrated [3], In our opinion this would be a possible explanation for their antipsoriatic activity. Following this hypothesis, difficultly hydrolizable 10-mono-substituted dithranol derivatives should not have any antipsoriatic activity.…”

Section: Introductionmentioning

confidence: 66%

Dithranol: Further Investigations on the Structure-Activity-Relationship

Schaltegger¹,

Brunner²,

Steiger³

et al. 1987

Dermatology

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The in vitro stability of 10-ethyldithranol (1,8-dihydroxy-10-ethyl-9(10H)-anthracenone) and its effects on healthy and psoriatic skin is investigated. 10-Ethyldithranol as a representative of the new class of 10-alkyldithranol derivatives neither stains nor irritates and has no antipsoriatic activity at all. This is due to the relatively stable substituent at carbon 10 which enables the fast oxidation processes necessary for the antipsoriatic effect. Therefore, antipsoriatically active dithranol derivatives require a free or easily liberated 10-position and hence the so-called ‘minimum structure of antipsoriatic anthrones’ keeps its validity.

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Oxidation of Antipsoriatic 10‐Acyldithranol Derivatives and Dithranol to 1,8‐Dihydroxyanthraquinone

Taskinen

Haarala

Wartiovaara

et al. 1988

Archiv der Pharmazie

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Decompositions of dithranol and butantrone (10-butyryldithranol) were studied in buffer solutions. Half lives at pH 9.4, 7.4 and 6.5 were 0.6, 1.2 and 3.0 h for dithranol, and 1.3, 15 and 30 h for butantrone, respectively. 1,8-Dihydroxyanthraquinone accounted for 50 % of the decomposition products from dithranol and for 20 % of those from butantrone at pH 9.4. Dithranol was not found as the decomposition product of butantrone. Based on kinetic considerations it is suggested that butantrone anion rather than dithranol anion is the intermediate of the main reaction in the oxidation of butantrone to 1,8-dihydroxyanthraquinone. Dithranol (anthralin, l&dihydroxyanthrone) has been the mainstay of topical treatment of psoriasis for over 60 years. Dithranol does, however, irritate the skin when oxidized and, apart from being therapeutically inactive, the final oxidation products also cause staining of the skin and clothing. The major decomposition and polymerization products are shown in Fig. 1. The detailed mechanism of the antipsoriatic activity of dithranol and its derivatives is not known. The minimum structural requirement for activity is proposed by Krebs and SchaZtegger3)to be a free methylene group at C-10. Because 10-acyl derivatives do not fulfil this requirement, they are supposed to be pro-drugs of dithranol cleaved in the skin to their parent compound4! Instead of dithranol Schaitegger and co-workers found in their study of in vitro hydrolysis of 10-acyl dithranols one of the oxidation products of dithranol, 1,8-dihydroxy anthraquinone. It was concluded that dithrano1 formed from 10-acyl derivatives is oxidized too quickly to be detected.From the point of view of structure-activity relationship of dithranol derivatives and the mechanism of their antipsoriatic activity it is of great interest to know whether 10-acyl dithranol derivatives are hydrolyzed to dithranol and at what rate. Therefore, a more quantitative study was undertaken on the in vitro decomposition of dithranol and 10-butyryl dithranol and on the formation of 1,8-dihydroxyanthraquinone.Recently, several 10-acylated derivatives of dithranol have been developed and tested in Finland as potential autipsoriatics ', 2! 10-Butyryl dithranol (butantrone, INN) is the best in terms Of to dithranol in antipsoriatic efficacy. In these 1 0-acylated derivatives of dithranol the acYl group diminishes considerably the formation of coloured oxidation products, they are therefore less staining.used without further purification. Experimental part CompoundsButantrone was synthesized at Orion Pharmaceutica. Dithranol was BP quality, 1,8-dihydroxyanthraquinone was purchased from Fluka AG (Bruchs, Switzerland), and the glucose used for buffer solution was Ph. Eur. quality. All the other chemicals and reagents were reagent grade, 104Halmekoski and Coworkers BuffersThe buffers were phosphate (pH 6.5 and 7.4) and N-2-hydroxyethylpiperazine-N-ethanesulfonic acid (Hepes, pH 9.4) buffers. The phosphate buffers were prepared by mixing 0.2 M disodium phosphate and 0.1 M ci...

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On the Stability of Some Antipsoriatic Active Anthralin (Dithranol) Derivatives

Cited by 8 publications

References 1 publication

An ESR study of thermal and photo-induced formation of radicals from anthralin and acylated derivatives

An ESR study of thermal and photo-induced formation of radicals from anthralin and acylated derivatives

Dithranol: Further Investigations on the Structure-Activity-Relationship

Oxidation of Antipsoriatic 10‐Acyldithranol Derivatives and Dithranol to 1,8‐Dihydroxyanthraquinone

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