Syntheses and evaluation of the antioxidant activity of acitretin analogs with amide bond(s) in the polyene spacer

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• 作者：Dimitra Hadjipavlou-Litina ; George E. Magoulas ; Marios Krokidis ; Dionissios Papaioannou
• 关键词：Retinoid ; Acitretin analog ; Antioxidant activity ; Anti-inflammatory activity ; Lipoxygenase inhibitor ; Lipid peroxidation
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2010
• 出版时间：January 2010
• 年：2010
• 卷：45
• 期：1
• 页码：298-310
• 全文大小：438 K

文摘

Ester analogs of the antipsoriatic drug acitretin were synthesized by coupling either anilines with N-protected indole-3-carboxylic acid, followed by deprotection and coupling with O-monoprotected dicarboxylic acids or Wittig reaction of indole-3-carboxaldehyde, 3-acetyl-1-tosylpyrrole and 4-amino-9-fluorenone with Ph₃PCHCO₂tBu, followed by N-deprotection, where necessary, and finally coupling with cinnamoyl fluorides. Corresponding free acids were obtained through TFA-mediated carboxyl group deprotection. Although these analogs and acitretin showed very low reducing abilities, analogs 5, 6, 8 and 12 strongly inhibited LOX with IC₅₀ values ranging from 35–65 μM. Acitretin and its analogs 5–7, 10, 11 and 15 inhibited lipid peroxidation more strongly than trolox whereas acitretin and analog 4 were in vivo more potent anti-inflammatory agents on rat paw oedema induced by Carrageenan than indomethacin.