10-phenylbutyryl-substituted anthracenones as inhibitors of keratinocyte growth and LTB4 biosynthesis

A recent observation that phenylbutyryl anthracenone 2, an analogue of the antipsoriatic anthralin, is a potent inhibitor of leukotriene B-4 (LTB4) bi osynthesis has prompted a search of other anthracenones with improved antip roliferative activity. In that direction, a limited number of analogues rel ated to 2 have been prepared and evaluated in the HaCaT keratinocytes proli feration and in the polymorphonuclear leukocyte LTB4 assay. The 4-methoxy a nalogue 2a and the side chain methylated 21 retain the full inhibitory acti vity of 1 against LTB4 biosynthesis while their antiproliferative activity is markedly enhanced and comparable to that of the antipsoriatic anthralin. In contrast to anthralin, cytotoxic effects against cell membranes are str ongly reduced as documented by the LDH activity released from cytoplasm of keratinocytes. (C) 2001 Editions scientifiques et medicales Elsevier SAS.