title: Potential antipsoriatic avarol derivatives as antioxidants and inhibitors of PGE(2) 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.
authors.affiliation: Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, Av. V. Andrés Estellés s/n, 46100, Burjassot, Valencia, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Amigó
authors.forename: Maria Carmen
authors.initials: MC
authors.lastname: Terencio
authors.forename: Maya
authors.initials: M
authors.lastname: Mitova
authors.forename: Carmine
authors.initials: C
authors.lastname: Iodice
authors.forename: Miguel
authors.initials: M
authors.lastname: Payá
authors.forename: Salvatore
authors.initials: S
authors.lastname: De Rosa
mesh_terms: D000975:Antioxidants / Q000138:chemical synthesis / Q000302:isolation & purification* / Q000494:pharmacology; D015232:Dinoprostone / Q000037:antagonists & inhibitors*; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000302:isolation & purification* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D007558:Italy; D015603:Keratinocytes / Q000187:drug effects / Q000201:enzymology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D012459:Salicylates / Q000138:chemical synthesis* / Q000494:pharmacology; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000302:isolation & purification* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000975:Antioxidants; D016166:Free Radical Scavengers; D012459:Salicylates; D012717:Sesquiterpenes; C493040:avarol-3'-thiosalicylate; D007770:L-Lactate Dehydrogenase; D015232:Dinoprostone; C023663:avarol