Abstract
A series of obtusatic acid analogues has been synthesized and evaluated as inhibitors of leukotriene B-4 (LTB4) biosynthesis and as antiproliferative agents. The 4-O-benzylated and the 4-O-demethylated congeners were the most potent inhibitors of LTB4 production of the depside class of compounds, with IC50 values in the submicromolar range. Furthermore, these compounds do not function as ...
Abstract
A series of obtusatic acid analogues has been synthesized and evaluated as inhibitors of leukotriene B-4 (LTB4) biosynthesis and as antiproliferative agents. The 4-O-benzylated and the 4-O-demethylated congeners were the most potent inhibitors of LTB4 production of the depside class of compounds, with IC50 values in the submicromolar range. Furthermore, these compounds do not function as redox-based inhibitors because they were not reactive against a stable free radical, 2,2-diphenyl-1-picrylhydrazyl, and did not produce appreciable amounts of deoxyribose degradation as a measure of their potency to generate hydroxyl radicals. Some obtusatic acid congeners were also potent inhibitors of keratinocyte growth. Growth inhibition was not mediated by damage to the cell membrane, as the activity of lactate dehydrogenase released from the cytoplasm was in the control range. (C) 2000 Editions scientifiques et medicales Elsevier SAS.
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