Antipsoriatic anthrones with modulated redox properties. 3. 10-Thio- substituted 1,8-dihydroxy-9(10H)-anthracenones as inhibitors of keratinocyte growth, 5-lipoxygenase, and the formation of 12(S)-HETE in mouse epidermis

Klaus Müller, Hsu Shan Huang, Wolfgang Wiegrebe

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34 Citations (Scopus)

Abstract

The synthesis of a series of 1,8-dihydroxy-9(10H)-anthracenones bearing sulfur-linked substituents in the 10-position is described. These compounds were evaluated for their ability to inhibit the growth of the human keratinocyte cell line HaCaT and the 5- and 12-lipoxygenase enzymes in bovine polymorphonuclear leukocytes and mouse epidermal homogenate, respectively. In addition, the following redox properties of the compounds were determined: reactivity against 2,2-diphenyl-1-picrylhydrazyl, generation of hydroxyl radicals as measured by deoxyribose degradation, and inhibition of lipid peroxidation in model membranes. Compounds 4e and 4h of this series compare favorably in the cellular assays with the antipsoriatic anthralin. They have the combined inhibitory action against leukotriene B4 and 12(S)-HETE formation and are highly potent antiproliferative agents against keratinocyte growth. In contrast to anthralin, 4h, 1,8-dihydroxy-10-[(4- hydroxyphenyl)thio]-9(10H)-anthracenone, is not cytotoxic as documented by the LDH activity released from cytoplasm of keratinocytes and does not enhance lipid peroxidation in model membranes.

Original languageEnglish
Pages (from-to)3132-3138
Number of pages7
JournalJournal of Medicinal Chemistry
Volume39
Issue number16
DOIs
Publication statusPublished - Aug 2 1996
Externally publishedYes

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Anthracenes
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
Anthralin
Arachidonate 5-Lipoxygenase
Growth Inhibitors
Keratinocytes
Epidermis
Oxidation-Reduction
Lipid Peroxidation
Bearings (structural)
Arachidonate 12-Lipoxygenase
Deoxyribose
Membranes
Lipids
Leukotriene B4
Growth
Sulfur
Hydroxyl Radical
Assays
Cytoplasm

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

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title = "Antipsoriatic anthrones with modulated redox properties. 3. 10-Thio- substituted 1,8-dihydroxy-9(10H)-anthracenones as inhibitors of keratinocyte growth, 5-lipoxygenase, and the formation of 12(S)-HETE in mouse epidermis",
abstract = "The synthesis of a series of 1,8-dihydroxy-9(10H)-anthracenones bearing sulfur-linked substituents in the 10-position is described. These compounds were evaluated for their ability to inhibit the growth of the human keratinocyte cell line HaCaT and the 5- and 12-lipoxygenase enzymes in bovine polymorphonuclear leukocytes and mouse epidermal homogenate, respectively. In addition, the following redox properties of the compounds were determined: reactivity against 2,2-diphenyl-1-picrylhydrazyl, generation of hydroxyl radicals as measured by deoxyribose degradation, and inhibition of lipid peroxidation in model membranes. Compounds 4e and 4h of this series compare favorably in the cellular assays with the antipsoriatic anthralin. They have the combined inhibitory action against leukotriene B4 and 12(S)-HETE formation and are highly potent antiproliferative agents against keratinocyte growth. In contrast to anthralin, 4h, 1,8-dihydroxy-10-[(4- hydroxyphenyl)thio]-9(10H)-anthracenone, is not cytotoxic as documented by the LDH activity released from cytoplasm of keratinocytes and does not enhance lipid peroxidation in model membranes.",
author = "Klaus M{\"u}ller and Huang, {Hsu Shan} and Wolfgang Wiegrebe",
year = "1996",
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T1 - Antipsoriatic anthrones with modulated redox properties. 3. 10-Thio- substituted 1,8-dihydroxy-9(10H)-anthracenones as inhibitors of keratinocyte growth, 5-lipoxygenase, and the formation of 12(S)-HETE in mouse epidermis

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AU - Huang, Hsu Shan

AU - Wiegrebe, Wolfgang

PY - 1996/8/2

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N2 - The synthesis of a series of 1,8-dihydroxy-9(10H)-anthracenones bearing sulfur-linked substituents in the 10-position is described. These compounds were evaluated for their ability to inhibit the growth of the human keratinocyte cell line HaCaT and the 5- and 12-lipoxygenase enzymes in bovine polymorphonuclear leukocytes and mouse epidermal homogenate, respectively. In addition, the following redox properties of the compounds were determined: reactivity against 2,2-diphenyl-1-picrylhydrazyl, generation of hydroxyl radicals as measured by deoxyribose degradation, and inhibition of lipid peroxidation in model membranes. Compounds 4e and 4h of this series compare favorably in the cellular assays with the antipsoriatic anthralin. They have the combined inhibitory action against leukotriene B4 and 12(S)-HETE formation and are highly potent antiproliferative agents against keratinocyte growth. In contrast to anthralin, 4h, 1,8-dihydroxy-10-[(4- hydroxyphenyl)thio]-9(10H)-anthracenone, is not cytotoxic as documented by the LDH activity released from cytoplasm of keratinocytes and does not enhance lipid peroxidation in model membranes.

AB - The synthesis of a series of 1,8-dihydroxy-9(10H)-anthracenones bearing sulfur-linked substituents in the 10-position is described. These compounds were evaluated for their ability to inhibit the growth of the human keratinocyte cell line HaCaT and the 5- and 12-lipoxygenase enzymes in bovine polymorphonuclear leukocytes and mouse epidermal homogenate, respectively. In addition, the following redox properties of the compounds were determined: reactivity against 2,2-diphenyl-1-picrylhydrazyl, generation of hydroxyl radicals as measured by deoxyribose degradation, and inhibition of lipid peroxidation in model membranes. Compounds 4e and 4h of this series compare favorably in the cellular assays with the antipsoriatic anthralin. They have the combined inhibitory action against leukotriene B4 and 12(S)-HETE formation and are highly potent antiproliferative agents against keratinocyte growth. In contrast to anthralin, 4h, 1,8-dihydroxy-10-[(4- hydroxyphenyl)thio]-9(10H)-anthracenone, is not cytotoxic as documented by the LDH activity released from cytoplasm of keratinocytes and does not enhance lipid peroxidation in model membranes.

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