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

Abstract

The synthesis and structure-activity relationships for a series of 14 new avarol derivatives as antioxidants and inhibitors of cell proliferation and PGE(2) 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 PGE(2) generation in the human keratinocyte HaCaT cell line. Compound 7(3'-methylaminoavarone) presented the best antiproliferative profile, by the inhibition of (3)H-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.

Evaluation of the Activity of the Sponge Metabolites Avarol and Avarone and their Synthetic Derivatives Against Fouling Micro- and Macroorganisms

“…The redox couple avarol (1) and avarone (2), isolated for the first time from the sponge Dysidea avara by Minale and coworkers [25], has shown strong activity against mouse lymphoma cells [26][27][28], antiviral activity [29][30][31], antiinflammatory activity [32], antipsoriatic properties [33], as well as moderate antifungal and antibacterial activity against Gram-positive strains [34,35]. Intrigued by the wide range of biological activities of these metabolites and the fact that avarol (1) is biosynthesized in large amounts by the sponge, implying an important ecological role [36], we decided to investigate their antifouling activity and prepare a number of lipophilic derivatives that would reduce their solubility in sea water and improve their incorporation in a potential antifouling preparation.…”

Reactivity and Biological Activity of the Marine Sesquiterpene Hydroquinone Avarol and Related Compounds from Sponges of the Order Dictyoceratida

“…Antiinflammatory effects of avarol were also ascribed to its behaviour as chain-breaking antioxidant of the arachidonate cascade, and/or as a scavenger of radicals. Of particular interest is the anti-psoriasis activity of avarol and some of its and avarone derivatives [108].…”

RETRACTED ARTICLE: Further in vitro biological activity evaluation of amino-, thio- and ester-derivatives of avarol

“…Thio-avarol derivatives represent the majority of compounds tested; however, some amino-and ester-avarol derivatives have been included in the aforementioned screening as well. The synthesis of all derivatives screened were available from literature 6,8,9 .…”