A novel series of 2- and 3-substituted 1,8-dihydroxy-9(10H)-anthracenones were synthesized and tested for their inhibitory activity against 5-lipoxygenase (5-LO) in bovine polymorphonuclear leukocytes and the growth of human keratinocytes. Structure-activity relationships are discussed with respect to the following redox properties of the compounds: reactivity against 2,2-diphenyl-1-picrylhydrazyl, generation of hydroxyl radicals as measured by deoxyribose degradation, and inhibition of lipid peroxidation in model membranes. Inhibition of cell proliferation seemed to be related to these properties, whereas 5-LO inhibition was not. Within a class of structural analogs the activity against 5-LO, which was markedly improved as compared to that of the antipsoriatic drug anthralin, correlated well with the overall lipophilicity. Even though a number of compounds in this series enhanced oxidative damage to nonlipid molecules such as deoxyribose, their antioxidant properties predominate in membrane lipids. Among the prooxidant compounds were also the most potent antiproliferative agents (IC50 values in the 10(-7) M range).