Potential Antipsoriatic Avarol Derivatives as Antioxidants and Inhibitors of PGE2 Generation and Proliferation in the HaCaT Cell Line

The synthesis and structure−activity relationships for a series of 14 new avarol derivatives as antioxidants and inhibitors of cell proliferation and PGE2 generation in human keratinocytes are described. Compound 6 (thiosalicylic derivative) was the most potent inhibitor of superoxide generation in human neutrophils and also potently inhibited PGE2 generation in the human keratinocyte HaCaT cell line. Compound 7 (3'-methylaminoavarone) presented the best antiproliferative profile, by the inhibition of 3H-thymidine incorporation in HaCaT cells, with potency similar to the reference compound anthralin. None of the avarol derivatives showed any sign of cytotoxicity measured as LDH release in treated keratinocytes. The potency and pharmacological profile of derivatives are also discussed.