Antipsoriatic Anthrones with Modulated Redox Properties, 1. Novel 10-Substituted 1,8-Dihydroxy-9(10H)-anthracenones as Inhibitors of 5-Lipoxygenase

URN to cite this document:

urn:nbn:de:bvb:355-epub-157844 Copy

DOI to cite this document:

10.5283/epub.15784 Copy

Müller, K. ; Gürster, D. ; Piwek, S. ; Wiegrebe, Wolfgang

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Date of publication of this fulltext: 12 Jul 2010 07:53

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Details

Item type:	Article
Journal or Publication Title:	European Journal of Medicinal Chemistry
Publisher:	Elsevier
Volume:	36
Number of Issue or Book Chapter:	25
Page Range:	pp. 4099-4107
Date:	1993
Institutions:	Chemistry and Pharmacy > Institute of Pharmacy > Alumni or Retired Professors > Prof. Wiegrebe
Dewey Decimal Classification:	500 Science > 540 Chemistry & allied sciences
Status:	Published
Refereed:	Yes, this version has been refereed
Created at the University of Regensburg:	Unknown
Item ID:	15784

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Abstract

The syntheses, the biological evaluation, and the structure-activity relationships of a novel series of l,8-dihydroxy-9(10H)-anthracenones bearing acyl-, alkyl-, or alkylidene-linked aromatic substituents in the 10-position are described. The phenylacyl and phenylalkylidene analogs were far more potent inhibitors of 5-lipoxygenase (5-LO) from bovine polymorphonuclear leukocytes (IC50 values in ...

Abstract

The syntheses, the biological evaluation, and the structure-activity relationships of a novel series
of l,8-dihydroxy-9(10H)-anthracenones bearing acyl-, alkyl-, or alkylidene-linked aromatic
substituents in the 10-position are described. The phenylacyl and phenylalkylidene analogs were
far more potent inhibitors of 5-lipoxygenase (5-LO) from bovine polymorphonuclear leukocytes
(IC50 values in the 10- 7 M range) than the antipsoriatic drug anthralin, whereas phenylalkyl analogs
were only weak inhibitors. Among the active compounds were both potent generators of hydroxyl
radicals, as determined by deoxyribose degradation, and strong reducers of the stable free radical
2,2-diphenyl-1-picrylhydrazyl (DPPH). However, several derivatives of this series maintained
5-LO inhibitory activity but did not generate hydroxyl radicals and were not reactive with DPPH .
In particular, phenylacyl analogs were also 6 times more efficient in inhibition of lipid peroxidation
in model membranes than anthralin. Structure-activity relationships have shown that the presence
of free phenolic groups in the attached aromatic ring is beneficial but not required for 5-LO
inhibitory potency. The inhibitory potency in the 10-phenylacyl series increased with the length
of the acyl chain with three methylene units being the optimum, suggesting a specific enzyme
interaction which would not be expected for nonspecific redox inhibitors.

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Metadata last modified: 26 Nov 2020 08:45

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