Simple analogues of anthralin

Unusual specificity of structure and antiproliferative activity

Klaus Müller, Helge Prinz, Ingo Gawlik, Klaus Ziereis, Hsu Shan Huang

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Fifty-nine simple analogues of the antipsoriatic agent, anthralin, have been prepared by modifying the positions of the 1,8-hydroxyl groups, replacement of the hydroxyl groups, substitution at the oxygen functions, introduction of additional functional groups into various positions of the anthracenone nucleus, or removal of particular structural elements. The compounds were evaluated for their, antiproliferative action against human keratinocytes and inhibition of the generation of leukotriene B4 in polymorphonuclear leukocytes, which may be useful to resolve the proliferative and inflammatory aspects of psoriasis, respectively. Even though many anthracenones were more potent inhibitors of leukotriene biosynthesis than anthralin, none of the compounds was substantially more effective as this drug in suppressing keratinocyte cell growth. There is an absolute requirement for two hydroxyl groups peri to a hydrogen bond acceptor such as a keto or an imino group for high potency. In addition to further delineating the nature of the pharmacophore for this class of compounds, also naphthalenedione with a peri hydroxyl group was identified as a pharmacophore with antiproliferative activity against keratinocyte growth.

Original languageEnglish
Pages (from-to)3773-3780
Number of pages8
JournalJournal of Medicinal Chemistry
Volume40
Issue number23
DOIs
Publication statusPublished - 1997
Externally publishedYes

Fingerprint

Anthralin
Hydroxyl Radical
Keratinocytes
Naphthoquinones
Leukotriene B4
Leukotrienes
Biosynthesis
Cell growth
Growth
Psoriasis
Functional groups
Hydrogen
Hydrogen bonds
Neutrophils
Substitution reactions
Oxygen
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Simple analogues of anthralin : Unusual specificity of structure and antiproliferative activity. / Müller, Klaus; Prinz, Helge; Gawlik, Ingo; Ziereis, Klaus; Huang, Hsu Shan.

In: Journal of Medicinal Chemistry, Vol. 40, No. 23, 1997, p. 3773-3780.

Research output: Contribution to journalArticle

Müller, Klaus ; Prinz, Helge ; Gawlik, Ingo ; Ziereis, Klaus ; Huang, Hsu Shan. / Simple analogues of anthralin : Unusual specificity of structure and antiproliferative activity. In: Journal of Medicinal Chemistry. 1997 ; Vol. 40, No. 23. pp. 3773-3780.
@article{aafde3c379e6400b87fd36373526a4f3,
title = "Simple analogues of anthralin: Unusual specificity of structure and antiproliferative activity",
abstract = "Fifty-nine simple analogues of the antipsoriatic agent, anthralin, have been prepared by modifying the positions of the 1,8-hydroxyl groups, replacement of the hydroxyl groups, substitution at the oxygen functions, introduction of additional functional groups into various positions of the anthracenone nucleus, or removal of particular structural elements. The compounds were evaluated for their, antiproliferative action against human keratinocytes and inhibition of the generation of leukotriene B4 in polymorphonuclear leukocytes, which may be useful to resolve the proliferative and inflammatory aspects of psoriasis, respectively. Even though many anthracenones were more potent inhibitors of leukotriene biosynthesis than anthralin, none of the compounds was substantially more effective as this drug in suppressing keratinocyte cell growth. There is an absolute requirement for two hydroxyl groups peri to a hydrogen bond acceptor such as a keto or an imino group for high potency. In addition to further delineating the nature of the pharmacophore for this class of compounds, also naphthalenedione with a peri hydroxyl group was identified as a pharmacophore with antiproliferative activity against keratinocyte growth.",
author = "Klaus M{\"u}ller and Helge Prinz and Ingo Gawlik and Klaus Ziereis and Huang, {Hsu Shan}",
year = "1997",
doi = "10.1021/jm970292n",
language = "English",
volume = "40",
pages = "3773--3780",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "23",

}

TY - JOUR

T1 - Simple analogues of anthralin

T2 - Unusual specificity of structure and antiproliferative activity

AU - Müller, Klaus

AU - Prinz, Helge

AU - Gawlik, Ingo

AU - Ziereis, Klaus

AU - Huang, Hsu Shan

PY - 1997

Y1 - 1997

N2 - Fifty-nine simple analogues of the antipsoriatic agent, anthralin, have been prepared by modifying the positions of the 1,8-hydroxyl groups, replacement of the hydroxyl groups, substitution at the oxygen functions, introduction of additional functional groups into various positions of the anthracenone nucleus, or removal of particular structural elements. The compounds were evaluated for their, antiproliferative action against human keratinocytes and inhibition of the generation of leukotriene B4 in polymorphonuclear leukocytes, which may be useful to resolve the proliferative and inflammatory aspects of psoriasis, respectively. Even though many anthracenones were more potent inhibitors of leukotriene biosynthesis than anthralin, none of the compounds was substantially more effective as this drug in suppressing keratinocyte cell growth. There is an absolute requirement for two hydroxyl groups peri to a hydrogen bond acceptor such as a keto or an imino group for high potency. In addition to further delineating the nature of the pharmacophore for this class of compounds, also naphthalenedione with a peri hydroxyl group was identified as a pharmacophore with antiproliferative activity against keratinocyte growth.

AB - Fifty-nine simple analogues of the antipsoriatic agent, anthralin, have been prepared by modifying the positions of the 1,8-hydroxyl groups, replacement of the hydroxyl groups, substitution at the oxygen functions, introduction of additional functional groups into various positions of the anthracenone nucleus, or removal of particular structural elements. The compounds were evaluated for their, antiproliferative action against human keratinocytes and inhibition of the generation of leukotriene B4 in polymorphonuclear leukocytes, which may be useful to resolve the proliferative and inflammatory aspects of psoriasis, respectively. Even though many anthracenones were more potent inhibitors of leukotriene biosynthesis than anthralin, none of the compounds was substantially more effective as this drug in suppressing keratinocyte cell growth. There is an absolute requirement for two hydroxyl groups peri to a hydrogen bond acceptor such as a keto or an imino group for high potency. In addition to further delineating the nature of the pharmacophore for this class of compounds, also naphthalenedione with a peri hydroxyl group was identified as a pharmacophore with antiproliferative activity against keratinocyte growth.

UR - http://www.scopus.com/inward/record.url?scp=0030810208&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030810208&partnerID=8YFLogxK

U2 - 10.1021/jm970292n

DO - 10.1021/jm970292n

M3 - Article

VL - 40

SP - 3773

EP - 3780

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 23

ER -