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
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.