Tetramethyltetrahydro-1,4-anthrachinonebenzoic acid, a 5-lipoxygenase-inhibitor with cell differentiating. Activity, 1,4-naphthoquinones, XXVIII

Article abstract of DOI:10.3797/scipharm.aut-01-196

The combination of 5-lipoxygenase (5-LOX) inhibition and retinoid activity in one molecule could be a suitable tool for the topical psoriasis therapy. The anellation of the 5-LOX inhibitor 1 with the tetramethylcyclohexane moity to the arotinoid structure 2 does not fullfil this expectation. This compound was not able to differentiate HL-60 cells to granulocytes. The exchange of the 3,5-di-tert-butyl-4-hydroxyphenyl substituent by benzoic acid and the synthesis of 8 resulted in the loss of 5-LOX inhibition also. The construction of 10 by the introduction of an azo spacer between the anthraquinone moity and benzoic acid of 8 finally led to the expected compound: 10 was potent 5-LOX inhibitor and concomitant differentiated HL-60 cells as measured by the NBT test.