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

•Solubility and partition coefficient of daidzein were significantly improved by sulfonic acid esterification.•Daidzein-4′-acetoxyl-7-benzene sulfonate had anti-inflammatory activity at 10−2μM.•Daidzein-7-benzene sulfonate showed significant anti-oxidative effect at 100μM.•The derivatives significantly inhibited phosphorylation of JNK.•Sulfonic acid esterification is an efficient improvement strategy. 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 1μM and derivative 4 had at 0.01μM as 100μM daidzein. Compound 3 also showed significant anti-oxidative effect at 100μM 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.