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

Abstract

A series of 10-hydrocinnamoyl and 10-cinnamoyl-1,8-dihydroxy-9(10 H)-anthracenones has been synthesized and evaluated as inhibitors of leukotriene B 4 (LTB 4) biosynthesis and as antiproliferative agents. In the hydrocinnamoyl series, compounds with phenolic hydroxyl groups were less potent inhibitors of LTB 4 biosynthesis than their non-phenolic analogs, suggesting that a nonspecific redox interaction between the compounds and the active site Fe 3+ of 5-lipoxygenase or chelation of Fe 3+ 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 IC 50 values in the submicromolar range. Their activity in this assay was equivalent to that observed with the antipsoriatic anthralin, whereas unspecific cytotoxicity was largely reduced as documented by the activity of lactate dehydrogenase released from cytoplasm of keratinocytes.