Potential antipsoriatic avarol derivatives as antioxidants and inhibitors of PGE(2) 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 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.
Amigó
Maria
M
Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, Av. V. Andrés Estellés s/n, 46100, Burjassot, Valencia, Spain.
Terencio
Maria Carmen
MC
Mitova
Maya
M
Iodice
Carmine
C
Payá
Miguel
M
De Rosa
Salvatore
S
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
D000975:Antioxidants; D016166:Free Radical Scavengers; D012459:Salicylates; D012717:Sesquiterpenes; C493040:avarol-3'-thiosalicylate; D007770:L-Lactate Dehydrogenase; D015232:Dinoprostone; C023663:avarol