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

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-alpha-stimulated Caco-2 cells. Daidzein derivatives 2 and 3 showed the same anti-inflammatory effect at 1 mu M and derivative 4 had at 0.01 mu M as 100 mu M daidzein. Compound 3 also showed significant anti -oxidative effect at 100 mu M in H2O2-treated caco-2 cells. Treatment with daidzein and its derivatives significantly inhibited TNF-alpha-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. (C) 2017 Elsevier Ltd. All rights reserved.