Anti-inflammatory and anti-oxidative activities of daidzein and its sulfonic acid ester derivatives

Abstract

To improve the activity of the isoflavone daidzein (1) and to explore its structure-activity relationship, new daidzein sulfonic acid ester derivatives (2–4) were synthesized. All three derivatives showed significantly enhanced anti-inflammatory activities by 100–10,000-fold over that of the parent daidzein in TNF-α-stimulated Caco-2 cells. Daidzein derivatives 2 and 3 showed the same anti-inflammatory effect at 1 μM and derivative 4 had at 0.01 μM as 100 μM daidzein. Compound 3 also showed significant anti-oxidative effect at 100 μM in H2O2-treated caco-2 cells. Treatment with daidzein and its derivatives significantly inhibited TNF-α-induced phosphorylation of JNK. Results suggest that sulfonic acid esterification at 4′- and/or 7- position of daidzein can significantly improve its physicochemical and pharmaceutical properties, consequently the cellular uptake or absorption and ultimately the biological activities.

Keywords

• Daidzein sulfonic acid ester
• Lipid/water partition coefficient
• Caco-2 epithelial cell
• Anti-inflammatory activity
• JNK