10-hydrocinnamoyl- and 10-cinnamoyl-1,8-dihydroxy-9(10H)-anthracenones as inhibitors of leukotriene B-4 biosynthesis and HaCaT cell growth

Citation
K. Muller et al., 10-hydrocinnamoyl- and 10-cinnamoyl-1,8-dihydroxy-9(10H)-anthracenones as inhibitors of leukotriene B-4 biosynthesis and HaCaT cell growth, EUR J MED C, 33(12), 1998, pp. 969-973
Citations number
14
Categorie Soggetti
Chemistry & Analysis
Journal title
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
ISSN journal
02235234 → ACNP
Volume
33
Issue
12
Year of publication
1998
Pages
969 - 973
Database
ISI
SICI code
0223-5234(199812)33:12<969:1A1AI>2.0.ZU;2-9
Abstract
A series of 10-hydrocinnamoyl and 10-cinnamoyl-1,8-dihydroxy-9(10H)-anthrac enones has been synthesized and evaluated as inhibitors of leukotriene B-4 (LTB4) biosynthesis and as antiproliferative agents. In the hydrocinnamoyl series, compounds with phenolic hydroxyl groups were less potent inhibitors of LTB4 biosynthesis than their non-phenolic analogs, suggesting that a no nspecific redox interaction between the compounds and the active site Fe3of 5-lipoxygenase or chelation of Fe3+ is not responsible for the observed activity. Compounds bearing a 10-cinnamoyl group were somewhat less active than their less rigid dihydrocinnamoyl congeners. Many compounds were also potent inhibitors of the growth of HaCaT cells with IC50 values in the subm icromolar range. Their activity in this assay was equivalent to that observ ed with the antipsoriatic anthralin, whereas unspecific cytotoxicity was la rgely reduced as documented by the activity of lactate dehydrogenase releas ed from cytoplasm of keratinocytes. (C) Elsevier, Paris.