Synthesis and biological evaluation of pyranoisoflavone derivatives as anti-inflammatory agents

In this paper, barbigerone (1a) and its twenty-seven related structural analogues were synthesized via complementary synthetic routes and their anti-inflammatory effects on the expression of INF-alpha in LPS-stimulated splenocytes were evaluated. Among these compounds, 1a, 1d, 1f and 1g were found to remarkably inhibit TNF-alpha production. Furthermore, 1g showed the most potent and dose-dependent manner inhibitory effect on INF-alpha release, with better IC50 value (3.58 mu M) than barbigerone (8.46 mu M). Oral administration of 1g at 20 mg/kg/day for two weeks obviously demonstrated protective effect in adjuvant-induced arthritis models as evaluated by clinical score of paws, and histological examination of joint tissues from rats. Mechanism studies on mRNA and protein level suggested that 1g inhibited the INF-alpha production via depressing INF-alpha converting enzyme (TACE) mRNA expression. In conclusion, these data show 1g with potential therapeutic effects as an anti-inflammatory agent. (c) 2014 Elsevier B.V. All rights reserved